MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling
Identifieur interne : 000667 ( Main/Exploration ); précédent : 000666; suivant : 000668MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling
Auteurs : Ping Jin [République populaire de Chine] ; Jingwen Jiang [République populaire de Chine] ; Na Xie [République populaire de Chine] ; Li Zhou [République populaire de Chine] ; Zhao Huang [République populaire de Chine] ; Lu Zhang [République populaire de Chine] ; Siyuan Qin [République populaire de Chine] ; Shuyue Fu [République populaire de Chine] ; Liyuan Peng [République populaire de Chine] ; Wei Gao [République populaire de Chine] ; Bowen Li [République populaire de Chine] ; Yunlong Lei [République populaire de Chine] ; Edouard C. Nice ; Changlong Li [République populaire de Chine] ; Jichun Shao ; Ke XieSource :
- Cell Death & Disease [ 2041-4889 ] ; 2019.
Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Development of novel chemotherapeutics is still required to enable successful treatment and improve survival for CRC patients. Here, we found that osimertinib (OSI) exhibits potent anti-CRC effects by inducing apoptosis, independent of its selective inhibitory activity targeting the EGFR T790M mutation. Intriguingly, OSI treatment triggers autophagic flux in CRC cells. Inhibition of autophagy markedly augments OSI-induced apoptosis and growth inhibition in CRC cells, suggesting a protective role of autophagy in response to OSI treatment. Mechanistically, OSI upregulates the expression of monocarboxylate transporter 1 (MCT1) and subsequently activates LKB1/AMPK signaling, leading to autophagy induction in CRC cells. Notably, OSI significantly exaggerates the sensitivity of CRC cells to the first-line drugs 5-fluorouracil or oxaliplatin. Taken together, our study unravels a novel mechanism of OSI-mediated protective autophagy involving MCT1/LKB1/AMPK signaling, and suggests the use of OSI as a potential agent for clinical CRC treatment.
Url:
DOI: 10.1038/s41419-019-1844-2
PubMed: 31409796
PubMed Central: 6692318
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000069
- to stream Pmc, to step Curation: 000069
- to stream Pmc, to step Checkpoint: 000617
- to stream Ncbi, to step Merge: 000907
- to stream Ncbi, to step Curation: 000907
- to stream Ncbi, to step Checkpoint: 000907
- to stream Main, to step Merge: 000667
- to stream Main, to step Curation: 000667
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling</title><author><name sortKey="Jin, Ping" sort="Jin, Ping" uniqKey="Jin P" first="Ping" last="Jin">Ping Jin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Jingwen" sort="Jiang, Jingwen" uniqKey="Jiang J" first="Jingwen" last="Jiang">Jingwen Jiang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Na" sort="Xie, Na" uniqKey="Xie N" first="Na" last="Xie">Na Xie</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Li" sort="Zhou, Li" uniqKey="Zhou L" first="Li" last="Zhou">Li Zhou</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Zhao" sort="Huang, Zhao" uniqKey="Huang Z" first="Zhao" last="Huang">Zhao Huang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Lu" sort="Zhang, Lu" uniqKey="Zhang L" first="Lu" last="Zhang">Lu Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Siyuan" sort="Qin, Siyuan" uniqKey="Qin S" first="Siyuan" last="Qin">Siyuan Qin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Shuyue" sort="Fu, Shuyue" uniqKey="Fu S" first="Shuyue" last="Fu">Shuyue Fu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Liyuan" sort="Peng, Liyuan" uniqKey="Peng L" first="Liyuan" last="Peng">Liyuan Peng</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Wei" sort="Gao, Wei" uniqKey="Gao W" first="Wei" last="Gao">Wei Gao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Li, Bowen" sort="Li, Bowen" uniqKey="Li B" first="Bowen" last="Li">Bowen Li</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Yunlong" sort="Lei, Yunlong" uniqKey="Lei Y" first="Yunlong" last="Lei">Yunlong Lei</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8653 0555</institution-id><institution-id institution-id-type="GRID">grid.203458.8</institution-id><institution>Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center,</institution><institution>Chongqing Medical University,</institution></institution-wrap>Chongqing, 400016 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Nice, Edouard C" sort="Nice, Edouard C" uniqKey="Nice E" first="Edouard C." last="Nice">Edouard C. Nice</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7857</institution-id><institution-id institution-id-type="GRID">grid.1002.3</institution-id><institution>Department of Biochemistry and Molecular Biology,</institution><institution>Monash University,</institution></institution-wrap>Clayton, VIC 3800 Australia</nlm:aff><wicri:noCountry code="subfield">VIC 3800 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Li, Changlong" sort="Li, Changlong" uniqKey="Li C" first="Changlong" last="Li">Changlong Li</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University,</institution></institution-wrap>Chengdu, 610041 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Shao, Jichun" sort="Shao, Jichun" uniqKey="Shao J" first="Jichun" last="Shao">Jichun Shao</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 3643</institution-id><institution-id institution-id-type="GRID">grid.413856.d</institution-id><institution>Department of Urology,</institution><institution>Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital),</institution></institution-wrap>Chengdu, Sichuan China</nlm:aff><wicri:noCountry code="subfield">Sichuan China</wicri:noCountry></affiliation></author><author><name sortKey="Xie, Ke" sort="Xie, Ke" uniqKey="Xie K" first="Ke" last="Xie">Ke Xie</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0369 4060</institution-id><institution-id institution-id-type="GRID">grid.54549.39</institution-id><institution>Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine,</institution><institution>University of Electronic Science and Technology of China,</institution></institution-wrap>Chengdu, Sichuan 610054 P. R. China</nlm:aff><wicri:noCountry code="subfield">Sichuan 610054 P. R. China</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31409796</idno><idno type="pmc">6692318</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692318</idno><idno type="RBID">PMC:6692318</idno><idno type="doi">10.1038/s41419-019-1844-2</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000069</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000069</idno><idno type="wicri:Area/Pmc/Curation">000069</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000069</idno><idno type="wicri:Area/Pmc/Checkpoint">000617</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000617</idno><idno type="wicri:Area/Ncbi/Merge">000907</idno><idno type="wicri:Area/Ncbi/Curation">000907</idno><idno type="wicri:Area/Ncbi/Checkpoint">000907</idno><idno type="wicri:Area/Main/Merge">000667</idno><idno type="wicri:Area/Main/Curation">000667</idno><idno type="wicri:Area/Main/Exploration">000667</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling</title><author><name sortKey="Jin, Ping" sort="Jin, Ping" uniqKey="Jin P" first="Ping" last="Jin">Ping Jin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Jingwen" sort="Jiang, Jingwen" uniqKey="Jiang J" first="Jingwen" last="Jiang">Jingwen Jiang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Na" sort="Xie, Na" uniqKey="Xie N" first="Na" last="Xie">Na Xie</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Li" sort="Zhou, Li" uniqKey="Zhou L" first="Li" last="Zhou">Li Zhou</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Zhao" sort="Huang, Zhao" uniqKey="Huang Z" first="Zhao" last="Huang">Zhao Huang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Lu" sort="Zhang, Lu" uniqKey="Zhang L" first="Lu" last="Zhang">Lu Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Siyuan" sort="Qin, Siyuan" uniqKey="Qin S" first="Siyuan" last="Qin">Siyuan Qin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Shuyue" sort="Fu, Shuyue" uniqKey="Fu S" first="Shuyue" last="Fu">Shuyue Fu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Liyuan" sort="Peng, Liyuan" uniqKey="Peng L" first="Liyuan" last="Peng">Liyuan Peng</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Gao, Wei" sort="Gao, Wei" uniqKey="Gao W" first="Wei" last="Gao">Wei Gao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Li, Bowen" sort="Li, Bowen" uniqKey="Li B" first="Bowen" last="Li">Bowen Li</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University, and Collaborative Innovation Center for Biotherapy,</institution></institution-wrap>Chengdu, 610041 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Yunlong" sort="Lei, Yunlong" uniqKey="Lei Y" first="Yunlong" last="Lei">Yunlong Lei</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8653 0555</institution-id><institution-id institution-id-type="GRID">grid.203458.8</institution-id><institution>Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center,</institution><institution>Chongqing Medical University,</institution></institution-wrap>Chongqing, 400016 P. R. China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Nice, Edouard C" sort="Nice, Edouard C" uniqKey="Nice E" first="Edouard C." last="Nice">Edouard C. Nice</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 7857</institution-id><institution-id institution-id-type="GRID">grid.1002.3</institution-id><institution>Department of Biochemistry and Molecular Biology,</institution><institution>Monash University,</institution></institution-wrap>Clayton, VIC 3800 Australia</nlm:aff><wicri:noCountry code="subfield">VIC 3800 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Li, Changlong" sort="Li, Changlong" uniqKey="Li C" first="Changlong" last="Li">Changlong Li</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 1581</institution-id><institution-id institution-id-type="GRID">grid.13291.38</institution-id><institution>West China School of Basic Medical Sciences & Forensic Medicine,</institution><institution>Sichuan University,</institution></institution-wrap>Chengdu, 610041 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chengdu</wicri:regionArea></affiliation></author><author><name sortKey="Shao, Jichun" sort="Shao, Jichun" uniqKey="Shao J" first="Jichun" last="Shao">Jichun Shao</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 3643</institution-id><institution-id institution-id-type="GRID">grid.413856.d</institution-id><institution>Department of Urology,</institution><institution>Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital),</institution></institution-wrap>Chengdu, Sichuan China</nlm:aff><wicri:noCountry code="subfield">Sichuan China</wicri:noCountry></affiliation></author><author><name sortKey="Xie, Ke" sort="Xie, Ke" uniqKey="Xie K" first="Ke" last="Xie">Ke Xie</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0369 4060</institution-id><institution-id institution-id-type="GRID">grid.54549.39</institution-id><institution>Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine,</institution><institution>University of Electronic Science and Technology of China,</institution></institution-wrap>Chengdu, Sichuan 610054 P. R. China</nlm:aff><wicri:noCountry code="subfield">Sichuan 610054 P. R. China</wicri:noCountry></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Development of novel chemotherapeutics is still required to enable successful treatment and improve survival for CRC patients. Here, we found that osimertinib (OSI) exhibits potent anti-CRC effects by inducing apoptosis, independent of its selective inhibitory activity targeting the EGFR T790M mutation. Intriguingly, OSI treatment triggers autophagic flux in CRC cells. Inhibition of autophagy markedly augments OSI-induced apoptosis and growth inhibition in CRC cells, suggesting a protective role of autophagy in response to OSI treatment. Mechanistically, OSI upregulates the expression of monocarboxylate transporter 1 (MCT1) and subsequently activates LKB1/AMPK signaling, leading to autophagy induction in CRC cells. Notably, OSI significantly exaggerates the sensitivity of CRC cells to the first-line drugs 5-fluorouracil or oxaliplatin. Taken together, our study unravels a novel mechanism of OSI-mediated protective autophagy involving MCT1/LKB1/AMPK signaling, and suggests the use of OSI as a potential agent for clinical CRC treatment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Poultsides, Ga" uniqKey="Poultsides G">GA Poultsides</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Gijn, W" uniqKey="Van Gijn W">W van Gijn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, L" uniqKey="He L">L He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Green, Dr" uniqKey="Green D">DR Green</name></author><author><name sortKey="Levine, B" uniqKey="Levine B">B Levine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, Gj" uniqKey="Yoshida G">GJ Yoshida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, Gj" uniqKey="Yoshida G">GJ Yoshida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toh, Ppc" uniqKey="Toh P">PPC Toh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raices, M" uniqKey="Raices M">M Raices</name></author><author><name sortKey="D Ngelo, Ma" uniqKey="D Ngelo M">MA D’Angelo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qian, H R" uniqKey="Qian H">H-R Qian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, Gj" uniqKey="Yoshida G">GJ Yoshida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cuff, M" uniqKey="Cuff M">M Cuff</name></author><author><name sortKey="Dyer, J" uniqKey="Dyer J">J Dyer</name></author><author><name sortKey="Jones, M" uniqKey="Jones M">M Jones</name></author><author><name sortKey="Shirazi Beechey, S" uniqKey="Shirazi Beechey S">S Shirazi-Beechey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinheiro, C" uniqKey="Pinheiro C">C Pinheiro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amorim, R" uniqKey="Amorim R">R Amorim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, Q" uniqKey="Fan Q">Q Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Politi, K" uniqKey="Politi K">K Politi</name></author><author><name sortKey="Ayeni, D" uniqKey="Ayeni D">D Ayeni</name></author><author><name sortKey="Lynch, T" uniqKey="Lynch T">T Lynch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Markman, B" uniqKey="Markman B">B Markman</name></author><author><name sortKey="Javier Ramos, F" uniqKey="Javier Ramos F">F Javier Ramos</name></author><author><name sortKey="Capdevila, J" uniqKey="Capdevila J">J Capdevila</name></author><author><name sortKey="Tabernero, J" uniqKey="Tabernero J">J Tabernero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghobrial, Im" uniqKey="Ghobrial I">IM Ghobrial</name></author><author><name sortKey="Witzig, Te" uniqKey="Witzig T">TE Witzig</name></author><author><name sortKey="Adjei, Aa" uniqKey="Adjei A">AA Adjei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mullard, A" uniqKey="Mullard A">A Mullard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sui, X" uniqKey="Sui X">X Sui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klionsky, Dj" uniqKey="Klionsky D">DJ Klionsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Onorati, Av" uniqKey="Onorati A">AV Onorati</name></author><author><name sortKey="Dyczynski, M" uniqKey="Dyczynski M">M Dyczynski</name></author><author><name sortKey="Ojha, R" uniqKey="Ojha R">R Ojha</name></author><author><name sortKey="Amaravadi, Rk" uniqKey="Amaravadi R">RK Amaravadi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zois, Ce" uniqKey="Zois C">CE Zois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jeong, Se Jin" uniqKey="Jeong S">Se-Jin Jeong</name></author><author><name sortKey="Zhang, Xiangyu" uniqKey="Zhang X">Xiangyu Zhang</name></author><author><name sortKey="Rodriguez Velez, Astrid" uniqKey="Rodriguez Velez A">Astrid Rodriguez-Velez</name></author><author><name sortKey="Evans, Trent D" uniqKey="Evans T">Trent D. Evans</name></author><author><name sortKey="Razani, Babak" uniqKey="Razani B">Babak Razani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeng, J" uniqKey="Zeng J">J Zeng</name></author><author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name></author><author><name sortKey="Fan, Yz" uniqKey="Fan Y">YZ Fan</name></author><author><name sortKey="He, Dl" uniqKey="He D">DL He</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dobrenel, T" uniqKey="Dobrenel T">T Dobrenel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miranda Goncalves, V" uniqKey="Miranda Goncalves V">V Miranda-Goncalves</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Zhang, M" uniqKey="Zhang M">M Zhang</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H Liu</name></author><author><name sortKey="Yin, W" uniqKey="Yin W">W Yin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tajima, A" uniqKey="Tajima A">A Tajima</name></author><author><name sortKey="Hess, Mt" uniqKey="Hess M">MT Hess</name></author><author><name sortKey="Cabrera, Bl" uniqKey="Cabrera B">BL Cabrera</name></author><author><name sortKey="Kolodner, Rd" uniqKey="Kolodner R">RD Kolodner</name></author><author><name sortKey="Carethers, Jm" uniqKey="Carethers J">JM Carethers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moutinho, C" uniqKey="Moutinho C">C Moutinho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, S" uniqKey="Wu S">S Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, L" uniqKey="Guo L">L Guo</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S Huang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cross, Da" uniqKey="Cross D">DA Cross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirano, T" uniqKey="Hirano T">T Hirano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kohli, L" uniqKey="Kohli L">L Kohli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeon, M" uniqKey="Yeon M">M Yeon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Zh" uniqKey="Tang Z">ZH Tang</name></author><author><name sortKey="Lu, Jj" uniqKey="Lu J">JJ Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Planchard, D" uniqKey="Planchard D">D Planchard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Zh" uniqKey="Tang Z">ZH Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eberlein, Ca" uniqKey="Eberlein C">CA Eberlein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodon, J" uniqKey="Rodon J">J Rodon</name></author><author><name sortKey="Dienstmann, R" uniqKey="Dienstmann R">R Dienstmann</name></author><author><name sortKey="Serra, V" uniqKey="Serra V">V Serra</name></author><author><name sortKey="Tabernero, J" uniqKey="Tabernero J">J Tabernero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chung, Sj" uniqKey="Chung S">SJ Chung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Semenza, Gl" uniqKey="Semenza G">GL Semenza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sonveaux, P" uniqKey="Sonveaux P">P Sonveaux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martins, Sf" uniqKey="Martins S">SF Martins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pola Ski, R" uniqKey="Pola Ski R">R Polański</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Nice, Edouard C" sort="Nice, Edouard C" uniqKey="Nice E" first="Edouard C." last="Nice">Edouard C. Nice</name><name sortKey="Shao, Jichun" sort="Shao, Jichun" uniqKey="Shao J" first="Jichun" last="Shao">Jichun Shao</name><name sortKey="Xie, Ke" sort="Xie, Ke" uniqKey="Xie K" first="Ke" last="Xie">Ke Xie</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Jin, Ping" sort="Jin, Ping" uniqKey="Jin P" first="Ping" last="Jin">Ping Jin</name></noRegion><name sortKey="Fu, Shuyue" sort="Fu, Shuyue" uniqKey="Fu S" first="Shuyue" last="Fu">Shuyue Fu</name><name sortKey="Gao, Wei" sort="Gao, Wei" uniqKey="Gao W" first="Wei" last="Gao">Wei Gao</name><name sortKey="Huang, Zhao" sort="Huang, Zhao" uniqKey="Huang Z" first="Zhao" last="Huang">Zhao Huang</name><name sortKey="Jiang, Jingwen" sort="Jiang, Jingwen" uniqKey="Jiang J" first="Jingwen" last="Jiang">Jingwen Jiang</name><name sortKey="Lei, Yunlong" sort="Lei, Yunlong" uniqKey="Lei Y" first="Yunlong" last="Lei">Yunlong Lei</name><name sortKey="Li, Bowen" sort="Li, Bowen" uniqKey="Li B" first="Bowen" last="Li">Bowen Li</name><name sortKey="Li, Changlong" sort="Li, Changlong" uniqKey="Li C" first="Changlong" last="Li">Changlong Li</name><name sortKey="Peng, Liyuan" sort="Peng, Liyuan" uniqKey="Peng L" first="Liyuan" last="Peng">Liyuan Peng</name><name sortKey="Qin, Siyuan" sort="Qin, Siyuan" uniqKey="Qin S" first="Siyuan" last="Qin">Siyuan Qin</name><name sortKey="Xie, Na" sort="Xie, Na" uniqKey="Xie N" first="Na" last="Xie">Na Xie</name><name sortKey="Zhang, Lu" sort="Zhang, Lu" uniqKey="Zhang L" first="Lu" last="Zhang">Lu Zhang</name><name sortKey="Zhou, Li" sort="Zhou, Li" uniqKey="Zhou L" first="Li" last="Zhou">Li Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000667 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000667 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:6692318
|texte= MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:31409796" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |