Heat shock protein 70 promotes HCC by modulating DNA-damage response, MAPK/ERK signaling and cellular senescence

Hdl Handle:
http://hdl.handle.net/10675.2/583142
Title:
Heat shock protein 70 promotes HCC by modulating DNA-damage response, MAPK/ERK signaling and cellular senescence
Authors:
Wang, Yan
Abstract:
The mechanisms that drive hepatocellular carcinoma (HCC) development are not well understood. Heat shock protein 70 (HSP70) plays a critical role in protein quality control. The HSP70-mediated response has been implicated in the development of different cancer types, however, the detailed mechanisms by which HSP70 supports tumor progression remains to be investigated. In this research work we observed that HSP70 deletion impairs HCC development by modulating the carcinogen-induced DNA damage response. This results in increased sensitivity to p53-dependent apoptosis, activation of MAPK/ERK negative feedback signaling pathway, and induction of cellular senescence. Inactivation of HSP70 may be a strategy to interfere with signaling pathways that drive liver cancer progression thus offering a therapeutic possibility for human HCC treatment. Note: The research data described in this Ph.D. Thesis are not published. Additional experimental work is needed to verify the data and solidify the mechanistic conclusions of this work before we seek publication of the data in a peer reviewed scientific journal. In light of new data generated from additional studies, we may need to modify or revised our mechanistic conclusions.
Affiliation:
Department of Biochemistry and Molecular Biology
Issue Date:
Oct-2015
URI:
http://hdl.handle.net/10675.2/583142
Type:
Dissertation
Appears in Collections:
Theses and Dissertations; Department of Neuroscience & Regenerative Medicine Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Yanen
dc.date.accessioned2015-12-02T18:58:44Zen
dc.date.available2015-12-02T18:58:44Zen
dc.date.issued2015-10en
dc.identifier.urihttp://hdl.handle.net/10675.2/583142en
dc.description.abstractThe mechanisms that drive hepatocellular carcinoma (HCC) development are not well understood. Heat shock protein 70 (HSP70) plays a critical role in protein quality control. The HSP70-mediated response has been implicated in the development of different cancer types, however, the detailed mechanisms by which HSP70 supports tumor progression remains to be investigated. In this research work we observed that HSP70 deletion impairs HCC development by modulating the carcinogen-induced DNA damage response. This results in increased sensitivity to p53-dependent apoptosis, activation of MAPK/ERK negative feedback signaling pathway, and induction of cellular senescence. Inactivation of HSP70 may be a strategy to interfere with signaling pathways that drive liver cancer progression thus offering a therapeutic possibility for human HCC treatment. Note: The research data described in this Ph.D. Thesis are not published. Additional experimental work is needed to verify the data and solidify the mechanistic conclusions of this work before we seek publication of the data in a peer reviewed scientific journal. In light of new data generated from additional studies, we may need to modify or revised our mechanistic conclusions.en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectCarcinoma, Hepatocellularen
dc.subjectHSP70 Heat-Shock Proteinsen
dc.subjectLiver Neoplasmsen
dc.titleHeat shock protein 70 promotes HCC by modulating DNA-damage response, MAPK/ERK signaling and cellular senescenceen
dc.typeDissertationen
dc.contributor.departmentDepartment of Biochemistry and Molecular Biologyen
dc.description.advisorMoskofidis, Dimitriosen
dc.description.committeeBieberich, Erhard; Horuzsko, Anatolij; Mivechi, Nahid; Schoenlein, Patricia; Manicassamy, Santhakumaren
dc.description.degreeDoctor of Philosophy with a Major in Molecular Medicineen
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.