Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy.
Identifieur interne : 000C20 ( Main/Merge ); précédent : 000C19; suivant : 000C21Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy.
Auteurs : Janice M. Santiago-O'Farrill [États-Unis] ; Eugenie S. Kleinerman [États-Unis] ; Mario G. Hollomon [États-Unis] ; Andrew Livingston [États-Unis] ; Wei-Lien Wang [États-Unis] ; Jen-Wei Tsai [États-Unis] ; Nancy B. Gordon [États-Unis]Source :
- Oncotarget [ 1949-2553 ] ; 2018.
Abstract
Autophagy is a catabolic process involved in cellular homeostasis. Autophagy is increased above homeostatic levels by chemotherapy, and this can either promote or inhibit tumor growth. We previously demonstrated that aerosol gemcitabine (GCB) has a therapeutic effect against osteosarcoma (OS) lung metastases. However, some tumor cells failed to respond to the treatment and persisted as isolated lung metastasis. Here, we examined the mechanisms underlying the dual role of chemotherapy-induced autophagy in OS and sought to identify biomarkers to predict OS response to treatment. In this study, we demonstrate that treatment of various OS cells with GCB induced autophagy. We also showed that GCB reduces the phosphorylation of AKT, mTOR and p70S6K and that GCB-induced autophagy in OS can lead to either cell survival or cell death. Blocking autophagy enhanced the sensitivity of LM7 OS cells and decreased the sensitivity of CCH-OS-D and K7M3 OS cells to GCB. Using a kinase array, we also demonstrated that differences in the phosphorylated heat shock protein 27 (p-HSP27) expression in the various OS cell lines after treatment with GCB, correlates to whether chemotherapy-induced autophagy will lead to increase or decrease OS cells sensitivity to therapy. Increased p-HSP27 was associated with increased sensitivity to anticancer drug treatment when autophagy is inhibited. The results of this study reveal a dual role of autophagy in OS cells sensitivity to chemotherapy and suggest that p-HSP27 could represent a predictive biomarker of whether combination therapy with autophagy modulators and chemotherapeutic drugs will be beneficial for OS patients.
DOI: 10.18632/oncotarget.20308
PubMed: 29416717
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000129
- to stream PubMed, to step Curation: 000129
- to stream PubMed, to step Checkpoint: 000093
- to stream Ncbi, to step Merge: 000424
- to stream Ncbi, to step Curation: 000424
- to stream Ncbi, to step Checkpoint: 000424
Links to Exploration step
pubmed:29416717Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy.</title>
<author><name sortKey="Santiago O Farrill, Janice M" sort="Santiago O Farrill, Janice M" uniqKey="Santiago O Farrill J" first="Janice M" last="Santiago-O'Farrill">Janice M. Santiago-O'Farrill</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kleinerman, Eugenie S" sort="Kleinerman, Eugenie S" uniqKey="Kleinerman E" first="Eugenie S" last="Kleinerman">Eugenie S. Kleinerman</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hollomon, Mario G" sort="Hollomon, Mario G" uniqKey="Hollomon M" first="Mario G" last="Hollomon">Mario G. Hollomon</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Biology, Texas Southern University, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biology, Texas Southern University, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Livingston, Andrew" sort="Livingston, Andrew" uniqKey="Livingston A" first="Andrew" last="Livingston">Andrew Livingston</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Wei Lien" sort="Wang, Wei Lien" uniqKey="Wang W" first="Wei-Lien" last="Wang">Wei-Lien Wang</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tsai, Jen Wei" sort="Tsai, Jen Wei" uniqKey="Tsai J" first="Jen-Wei" last="Tsai">Jen-Wei Tsai</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gordon, Nancy B" sort="Gordon, Nancy B" uniqKey="Gordon N" first="Nancy B" last="Gordon">Nancy B. Gordon</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2018">2018</date>
<idno type="RBID">pubmed:29416717</idno>
<idno type="pmid">29416717</idno>
<idno type="doi">10.18632/oncotarget.20308</idno>
<idno type="wicri:Area/PubMed/Corpus">000129</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000129</idno>
<idno type="wicri:Area/PubMed/Curation">000129</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000129</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000093</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000093</idno>
<idno type="wicri:Area/Ncbi/Merge">000424</idno>
<idno type="wicri:Area/Ncbi/Curation">000424</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">000424</idno>
<idno type="wicri:Area/Main/Merge">000C20</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy.</title>
<author><name sortKey="Santiago O Farrill, Janice M" sort="Santiago O Farrill, Janice M" uniqKey="Santiago O Farrill J" first="Janice M" last="Santiago-O'Farrill">Janice M. Santiago-O'Farrill</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kleinerman, Eugenie S" sort="Kleinerman, Eugenie S" uniqKey="Kleinerman E" first="Eugenie S" last="Kleinerman">Eugenie S. Kleinerman</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hollomon, Mario G" sort="Hollomon, Mario G" uniqKey="Hollomon M" first="Mario G" last="Hollomon">Mario G. Hollomon</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Biology, Texas Southern University, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biology, Texas Southern University, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Livingston, Andrew" sort="Livingston, Andrew" uniqKey="Livingston A" first="Andrew" last="Livingston">Andrew Livingston</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Wei Lien" sort="Wang, Wei Lien" uniqKey="Wang W" first="Wei-Lien" last="Wang">Wei-Lien Wang</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tsai, Jen Wei" sort="Tsai, Jen Wei" uniqKey="Tsai J" first="Jen-Wei" last="Tsai">Jen-Wei Tsai</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gordon, Nancy B" sort="Gordon, Nancy B" uniqKey="Gordon N" first="Nancy B" last="Gordon">Nancy B. Gordon</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncotarget</title>
<idno type="eISSN">1949-2553</idno>
<imprint><date when="2018" type="published">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Autophagy is a catabolic process involved in cellular homeostasis. Autophagy is increased above homeostatic levels by chemotherapy, and this can either promote or inhibit tumor growth. We previously demonstrated that aerosol gemcitabine (GCB) has a therapeutic effect against osteosarcoma (OS) lung metastases. However, some tumor cells failed to respond to the treatment and persisted as isolated lung metastasis. Here, we examined the mechanisms underlying the dual role of chemotherapy-induced autophagy in OS and sought to identify biomarkers to predict OS response to treatment. In this study, we demonstrate that treatment of various OS cells with GCB induced autophagy. We also showed that GCB reduces the phosphorylation of AKT, mTOR and p70S6K and that GCB-induced autophagy in OS can lead to either cell survival or cell death. Blocking autophagy enhanced the sensitivity of LM7 OS cells and decreased the sensitivity of CCH-OS-D and K7M3 OS cells to GCB. Using a kinase array, we also demonstrated that differences in the phosphorylated heat shock protein 27 (p-HSP27) expression in the various OS cell lines after treatment with GCB, correlates to whether chemotherapy-induced autophagy will lead to increase or decrease OS cells sensitivity to therapy. Increased p-HSP27 was associated with increased sensitivity to anticancer drug treatment when autophagy is inhibited. The results of this study reveal a dual role of autophagy in OS cells sensitivity to chemotherapy and suggest that p-HSP27 could represent a predictive biomarker of whether combination therapy with autophagy modulators and chemotherapeutic drugs will be beneficial for OS patients.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C20 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 000C20 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= ChloroquineV1 |flux= Main |étape= Merge |type= RBID |clé= pubmed:29416717 |texte= Phosphorylated heat shock protein 27 as a potential biomarker to predict the role of chemotherapy-induced autophagy in osteosarcoma response to therapy. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:29416717" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a ChloroquineV1
This area was generated with Dilib version V0.6.33. |