TIPRL potentiates survival of lung cancer by inducing autophagy through the eIF2α-ATF4 pathway
Identifieur interne : 000405 ( Main/Exploration ); précédent : 000404; suivant : 000406TIPRL potentiates survival of lung cancer by inducing autophagy through the eIF2α-ATF4 pathway
Auteurs : Su-Jin Jeon [Corée du Sud] ; Jun-Ho Ahn [Corée du Sud] ; Debasish Halder [Corée du Sud] ; Hyun-Soo Cho [Corée du Sud] ; Jung-Hwa Lim [Corée du Sud] ; Soo Young Jun [Corée du Sud] ; Jeong-Ju Lee [Corée du Sud] ; Ji-Yong Yoon [Corée du Sud] ; Min-Hyuk Choi [Corée du Sud] ; Cho-Rok Jung [Corée du Sud] ; Jin-Man Kim [Corée du Sud] ; Nam-Soon Kim [Corée du Sud]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2019.
Abstract
Autophagy, an intracellular system of degrading damaged organelles and misfolded proteins, is essential for cancer cell survival. Despite the progress made towards understanding the mechanism, identification of novel autophagy regulators presents a major obstacle in developing anticancer therapies. Here, we examine the association between the TOR signaling pathway regulator-like (TIPRL) protein and autophagy in malignant transformation of tumors. We show that TIPRL upregulation in non-small cell lung cancer (NSCLC) potentiated autophagy activity and enabled autophagic clearance of metabolic and cellular stress, conferring a survival advantage to cancer cells. Importantly, the interaction of TIPRL with eukaryotic initiation factor 2α (eIF2α) led to eIF2α phosphorylation and activation of the eIF2α-ATF4 pathway, thereby inducing autophagy. Conversely, TIPRL depletion increased apoptosis by reducing autophagic clearance, which was markedly enhanced in TIPRL-depleted A549 xenografts treated with 2-deoxy-D-glucose. Overall, the study indicated that TIPRL is a potential regulator of autophagy and an important drug target for lung cancer therapy.
Url:
DOI: 10.1038/s41419-019-2190-0
PubMed: 31862913
PubMed Central: 6925247
Affiliations:
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</author>
<author><name sortKey="Lim, Jung Hwa" sort="Lim, Jung Hwa" uniqKey="Lim J" first="Jung-Hwa" last="Lim">Jung-Hwa Lim</name>
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<institution-id institution-id-type="GRID">grid.412786.e</institution-id>
<institution>Department of Functional Genomics, KRIBB School of Bioscience,</institution>
<institution>University of Science and Technology (UST),</institution>
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217 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
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125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
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</affiliation>
</author>
<author><name sortKey="Jun, Soo Young" sort="Jun, Soo Young" uniqKey="Jun S" first="Soo Young" last="Jun">Soo Young Jun</name>
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<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
<institution>Genome Research Center,</institution>
<institution>Korea Research Institute of Bioscience and Biotechnology (KRIBB),</institution>
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125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
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</affiliation>
</author>
<author><name sortKey="Lee, Jeong Ju" sort="Lee, Jeong Ju" uniqKey="Lee J" first="Jeong-Ju" last="Lee">Jeong-Ju Lee</name>
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<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
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<institution>Korea Research Institute of Bioscience and Biotechnology (KRIBB),</institution>
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125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
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<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yoon, Ji Yong" sort="Yoon, Ji Yong" uniqKey="Yoon J" first="Ji-Yong" last="Yoon">Ji-Yong Yoon</name>
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<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
<institution>Genome Research Center,</institution>
<institution>Korea Research Institute of Bioscience and Biotechnology (KRIBB),</institution>
</institution-wrap>
125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>125 Gwahak-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Choi, Min Hyuk" sort="Choi, Min Hyuk" uniqKey="Choi M" first="Min-Hyuk" last="Choi">Min-Hyuk Choi</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0636 3099</institution-id>
<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
<institution>Genome Research Center,</institution>
<institution>Korea Research Institute of Bioscience and Biotechnology (KRIBB),</institution>
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125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>125 Gwahak-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
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<institution>Department of Functional Genomics, KRIBB School of Bioscience,</institution>
<institution>University of Science and Technology (UST),</institution>
</institution-wrap>
217 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>217 Gajeong-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jung, Cho Rok" sort="Jung, Cho Rok" uniqKey="Jung C" first="Cho-Rok" last="Jung">Cho-Rok Jung</name>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1791 8264</institution-id>
<institution-id institution-id-type="GRID">grid.412786.e</institution-id>
<institution>Department of Functional Genomics, KRIBB School of Bioscience,</institution>
<institution>University of Science and Technology (UST),</institution>
</institution-wrap>
217 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>217 Gajeong-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0636 3099</institution-id>
<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
<institution>Gene Therapy Research Unit,</institution>
<institution>Korea Research Institute of Bioscience and Biotechnology,</institution>
</institution-wrap>
125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>125 Gwahak-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Jin Man" sort="Kim, Jin Man" uniqKey="Kim J" first="Jin-Man" last="Kim">Jin-Man Kim</name>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0722 6377</institution-id>
<institution-id institution-id-type="GRID">grid.254230.2</institution-id>
<institution>Department of Pathology, School of Medicine,</institution>
<institution>Chungnam National University,</institution>
</institution-wrap>
99 Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>99 Daehak-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Nam Soon" sort="Kim, Nam Soon" uniqKey="Kim N" first="Nam-Soon" last="Kim">Nam-Soon Kim</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0636 3099</institution-id>
<institution-id institution-id-type="GRID">grid.249967.7</institution-id>
<institution>Genome Research Center,</institution>
<institution>Korea Research Institute of Bioscience and Biotechnology (KRIBB),</institution>
</institution-wrap>
125 Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>125 Gwahak-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1791 8264</institution-id>
<institution-id institution-id-type="GRID">grid.412786.e</institution-id>
<institution>Department of Functional Genomics, KRIBB School of Bioscience,</institution>
<institution>University of Science and Technology (UST),</institution>
</institution-wrap>
217 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>217 Gajeong-ro, Yuseong-gu, Daejeon</wicri:regionArea>
<wicri:noRegion>Daejeon</wicri:noRegion>
</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>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="Par1">Autophagy, an intracellular system of degrading damaged organelles and misfolded proteins, is essential for cancer cell survival. Despite the progress made towards understanding the mechanism, identification of novel autophagy regulators presents a major obstacle in developing anticancer therapies. Here, we examine the association between the TOR signaling pathway regulator-like (TIPRL) protein and autophagy in malignant transformation of tumors. We show that TIPRL upregulation in non-small cell lung cancer (NSCLC) potentiated autophagy activity and enabled autophagic clearance of metabolic and cellular stress, conferring a survival advantage to cancer cells. Importantly, the interaction of TIPRL with eukaryotic initiation factor 2α (eIF2α) led to eIF2α phosphorylation and activation of the eIF2α-ATF4 pathway, thereby inducing autophagy. Conversely, TIPRL depletion increased apoptosis by reducing autophagic clearance, which was markedly enhanced in TIPRL-depleted A549 xenografts treated with 2-deoxy-D-glucose. Overall, the study indicated that TIPRL is a potential regulator of autophagy and an important drug target for lung cancer therapy.</p>
</div>
</front>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Corée du Sud</li>
</country>
</list>
<tree><country name="Corée du Sud"><noRegion><name sortKey="Jeon, Su Jin" sort="Jeon, Su Jin" uniqKey="Jeon S" first="Su-Jin" last="Jeon">Su-Jin Jeon</name>
</noRegion>
<name sortKey="Ahn, Jun Ho" sort="Ahn, Jun Ho" uniqKey="Ahn J" first="Jun-Ho" last="Ahn">Jun-Ho Ahn</name>
<name sortKey="Ahn, Jun Ho" sort="Ahn, Jun Ho" uniqKey="Ahn J" first="Jun-Ho" last="Ahn">Jun-Ho Ahn</name>
<name sortKey="Cho, Hyun Soo" sort="Cho, Hyun Soo" uniqKey="Cho H" first="Hyun-Soo" last="Cho">Hyun-Soo Cho</name>
<name sortKey="Cho, Hyun Soo" sort="Cho, Hyun Soo" uniqKey="Cho H" first="Hyun-Soo" last="Cho">Hyun-Soo Cho</name>
<name sortKey="Choi, Min Hyuk" sort="Choi, Min Hyuk" uniqKey="Choi M" first="Min-Hyuk" last="Choi">Min-Hyuk Choi</name>
<name sortKey="Choi, Min Hyuk" sort="Choi, Min Hyuk" uniqKey="Choi M" first="Min-Hyuk" last="Choi">Min-Hyuk Choi</name>
<name sortKey="Halder, Debasish" sort="Halder, Debasish" uniqKey="Halder D" first="Debasish" last="Halder">Debasish Halder</name>
<name sortKey="Jeon, Su Jin" sort="Jeon, Su Jin" uniqKey="Jeon S" first="Su-Jin" last="Jeon">Su-Jin Jeon</name>
<name sortKey="Jun, Soo Young" sort="Jun, Soo Young" uniqKey="Jun S" first="Soo Young" last="Jun">Soo Young Jun</name>
<name sortKey="Jung, Cho Rok" sort="Jung, Cho Rok" uniqKey="Jung C" first="Cho-Rok" last="Jung">Cho-Rok Jung</name>
<name sortKey="Jung, Cho Rok" sort="Jung, Cho Rok" uniqKey="Jung C" first="Cho-Rok" last="Jung">Cho-Rok Jung</name>
<name sortKey="Kim, Jin Man" sort="Kim, Jin Man" uniqKey="Kim J" first="Jin-Man" last="Kim">Jin-Man Kim</name>
<name sortKey="Kim, Nam Soon" sort="Kim, Nam Soon" uniqKey="Kim N" first="Nam-Soon" last="Kim">Nam-Soon Kim</name>
<name sortKey="Kim, Nam Soon" sort="Kim, Nam Soon" uniqKey="Kim N" first="Nam-Soon" last="Kim">Nam-Soon Kim</name>
<name sortKey="Lee, Jeong Ju" sort="Lee, Jeong Ju" uniqKey="Lee J" first="Jeong-Ju" last="Lee">Jeong-Ju Lee</name>
<name sortKey="Lim, Jung Hwa" sort="Lim, Jung Hwa" uniqKey="Lim J" first="Jung-Hwa" last="Lim">Jung-Hwa Lim</name>
<name sortKey="Lim, Jung Hwa" sort="Lim, Jung Hwa" uniqKey="Lim J" first="Jung-Hwa" last="Lim">Jung-Hwa Lim</name>
<name sortKey="Yoon, Ji Yong" sort="Yoon, Ji Yong" uniqKey="Yoon J" first="Ji-Yong" last="Yoon">Ji-Yong Yoon</name>
</country>
</tree>
</affiliations>
</record>
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