Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes
Identifieur interne : 000451 ( Main/Exploration ); précédent : 000450; suivant : 000452Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes
Auteurs : Reshu Saxena ; Alena Klochkova ; Mary Grace Murray ; Mohammad Faujul Kabir ; Safiyah Samad ; Tyler Beccari ; Julie Gang ; Kishan Patel ; Kathryn E. Hamilton ; Kelly A. Whelan [États-Unis]Source :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
Esophageal cancer is among the most aggressive forms of human malignancy with five-year survival rates of <20%. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. While alterations in autophagy have been associated with carcinogenesis across tissues, cell type- and context-dependent roles for autophagy have been reported. Herein, we review the current knowledge related to autophagy in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the two most common subtypes of esophageal malignancy. We explore roles for autophagy in the development and progression of ESCC and EAC. We then continue to discuss molecular markers of autophagy as they relate to esophageal patient outcomes. Finally, we summarize current literature examining roles for autophagy in ESCC and EAC response to therapy and discuss considerations for the potential use of autophagy inhibitors as experimental therapeutics that may improve patient outcomes in esophageal cancer.
Url:
DOI: 10.3390/cancers11111697
PubMed: 31683722
PubMed Central: 6895837
Affiliations:
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Klochkova</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Murray, Mary Grace" sort="Murray, Mary Grace" uniqKey="Murray M" first="Mary Grace" last="Murray">Mary Grace Murray</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> 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(K.P.)</nlm:aff></affiliation></author><author><name sortKey="Samad, Safiyah" sort="Samad, Safiyah" uniqKey="Samad S" first="Safiyah" last="Samad">Safiyah Samad</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Beccari, Tyler" sort="Beccari, Tyler" uniqKey="Beccari T" first="Tyler" last="Beccari">Tyler Beccari</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Gang, Julie" sort="Gang, Julie" uniqKey="Gang J" first="Julie" last="Gang">Julie Gang</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Patel, Kishan" sort="Patel, Kishan" uniqKey="Patel K" first="Kishan" last="Patel">Kishan Patel</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Hamilton, Kathryn E" sort="Hamilton, Kathryn E" uniqKey="Hamilton K" first="Kathryn E." last="Hamilton">Kathryn E. Hamilton</name><affiliation><nlm:aff id="af2-cancers-11-01697">Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA;<email>HAMILTONK1@email.chop.edu</email></nlm:aff></affiliation></author><author><name sortKey="Whelan, Kelly A" sort="Whelan, Kelly A" uniqKey="Whelan K" first="Kelly A." last="Whelan">Kelly A. Whelan</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-cancers-11-01697">Department of Pathology & Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology & Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140</wicri:regionArea><wicri:noRegion>PA 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type="wicri:Area/Main/Curation">000451</idno><idno type="wicri:Area/Main/Exploration">000451</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes</title><author><name sortKey="Saxena, Reshu" sort="Saxena, Reshu" uniqKey="Saxena R" first="Reshu" last="Saxena">Reshu Saxena</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Klochkova, Alena" sort="Klochkova, Alena" uniqKey="Klochkova A" first="Alena" last="Klochkova">Alena Klochkova</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Murray, Mary Grace" sort="Murray, Mary Grace" uniqKey="Murray M" first="Mary Grace" last="Murray">Mary Grace Murray</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Kabir, Mohammad Faujul" sort="Kabir, Mohammad Faujul" uniqKey="Kabir M" first="Mohammad Faujul" last="Kabir">Mohammad Faujul Kabir</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Samad, Safiyah" sort="Samad, Safiyah" uniqKey="Samad S" first="Safiyah" last="Samad">Safiyah Samad</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Beccari, Tyler" sort="Beccari, Tyler" uniqKey="Beccari T" first="Tyler" last="Beccari">Tyler Beccari</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Gang, Julie" sort="Gang, Julie" uniqKey="Gang J" first="Julie" last="Gang">Julie Gang</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Patel, Kishan" sort="Patel, Kishan" uniqKey="Patel K" first="Kishan" last="Patel">Kishan Patel</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation></author><author><name sortKey="Hamilton, Kathryn E" sort="Hamilton, Kathryn E" uniqKey="Hamilton K" first="Kathryn E." last="Hamilton">Kathryn E. Hamilton</name><affiliation><nlm:aff id="af2-cancers-11-01697">Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA;<email>HAMILTONK1@email.chop.edu</email></nlm:aff></affiliation></author><author><name sortKey="Whelan, Kelly A" sort="Whelan, Kelly A" uniqKey="Whelan K" first="Kelly A." last="Whelan">Kelly A. Whelan</name><affiliation><nlm:aff id="af1-cancers-11-01697">Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA;<email>tuj81303@temple.edu</email> (R.S.);<email>tuj51051@temple.edu</email> (A.K.);<email>mary.murray337@gmail.com</email> (M.G.M.);<email>tul69249@temple.edu</email> (M.F.K.);<email>ssamad1999@gmail.com</email> (S.S.);<email>tbeccari@holyfamily.edu</email> (T.B.);<email>tug67451@temple.edu</email> (J.G.);<email>tug99040@temple.edu</email> (K.P.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-cancers-11-01697">Department of Pathology & Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology & Laboratory Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140</wicri:regionArea><wicri:noRegion>PA 19140</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</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>Esophageal cancer is among the most aggressive forms of human malignancy with five-year survival rates of <20%. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. While alterations in autophagy have been associated with carcinogenesis across tissues, cell type- and context-dependent roles for autophagy have been reported. Herein, we review the current knowledge related to autophagy in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the two most common subtypes of esophageal malignancy. We explore roles for autophagy in the development and progression of ESCC and EAC. We then continue to discuss molecular markers of autophagy as they relate to esophageal patient outcomes. Finally, we summarize current literature examining roles for autophagy in ESCC and EAC response to therapy and discuss considerations for the potential use of autophagy inhibitors as experimental therapeutics that may improve patient outcomes in esophageal cancer.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Fitzmaurice, C" uniqKey="Fitzmaurice C">C. Fitzmaurice</name></author><author><name sortKey="Dicker, D" uniqKey="Dicker D">D. Dicker</name></author><author><name sortKey="Pain, A" uniqKey="Pain A">A. Pain</name></author><author><name sortKey="Hamavid, H" uniqKey="Hamavid H">H. Hamavid</name></author><author><name sortKey="Moradi Lakeh, M" uniqKey="Moradi Lakeh M">M. Moradi-Lakeh</name></author><author><name sortKey="Macintyre, M F" uniqKey="Macintyre M">M.F. MacIntyre</name></author><author><name sortKey="Allen, C" uniqKey="Allen C">C. Allen</name></author><author><name sortKey="Hansen, G" uniqKey="Hansen G">G. 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Hamilton</name><name sortKey="Kabir, Mohammad Faujul" sort="Kabir, Mohammad Faujul" uniqKey="Kabir M" first="Mohammad Faujul" last="Kabir">Mohammad Faujul Kabir</name><name sortKey="Klochkova, Alena" sort="Klochkova, Alena" uniqKey="Klochkova A" first="Alena" last="Klochkova">Alena Klochkova</name><name sortKey="Murray, Mary Grace" sort="Murray, Mary Grace" uniqKey="Murray M" first="Mary Grace" last="Murray">Mary Grace Murray</name><name sortKey="Patel, Kishan" sort="Patel, Kishan" uniqKey="Patel K" first="Kishan" last="Patel">Kishan Patel</name><name sortKey="Samad, Safiyah" sort="Samad, Safiyah" uniqKey="Samad S" first="Safiyah" last="Samad">Safiyah Samad</name><name sortKey="Saxena, Reshu" sort="Saxena, Reshu" uniqKey="Saxena R" first="Reshu" last="Saxena">Reshu Saxena</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Whelan, Kelly A" sort="Whelan, Kelly A" uniqKey="Whelan K" first="Kelly A." last="Whelan">Kelly A. 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