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Articles 1 - 5 of 5
Full-Text Articles in Cancer Biology
Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder
Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder
Dissertations & Theses (Open Access)
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine, …
The Role Of P62/Sqstm1 In Tgfβ-Dependent Emt And Autophagy, Evelyn Ng
The Role Of P62/Sqstm1 In Tgfβ-Dependent Emt And Autophagy, Evelyn Ng
Electronic Thesis and Dissertation Repository
Transforming growth factor beta (TGFβ) is a cytokine that regulates cellular adhesion, proliferation and apoptosis. In the context of cancer, TGFβ induces processes such as epithelial-to-mesenchymal transition (EMT). More recently, TGFβ has been discovered to also induce autophagy, and the relationship between TGFβ-induced EMT and autophagy remains unknown. Due to its involvement in autophagy and its established interactions with key TGFβ signaling proteins, this thesis focuses on the sequestosome 1 (p62/SQSTM1) protein. Here, I have shown that p62/SQSTM1 co-localizes with TGFβ receptors at the same time point that the receptors localize to Rab7-positive late endosomes. siRNA-mediated silencing of p62/SQSTM1 was …
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Dissertations & Theses (Open Access)
Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …
The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton
The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton
Dissertations & Theses (Open Access)
DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the activation …
Adipocytes Activate Mitochondrial Fatty Acid Oxidation And Autophagy To Promote Tumor Growth In Colon Cancer, Yang-An Wen, Xiaopeng Xing, Jennifer W. Harris, Yekaterina Y. Zaytseva, Mihail I. Mitov, Dana L. Napier, Heidi L. Weiss, B. Mark Evers, Tianyan Gao
Adipocytes Activate Mitochondrial Fatty Acid Oxidation And Autophagy To Promote Tumor Growth In Colon Cancer, Yang-An Wen, Xiaopeng Xing, Jennifer W. Harris, Yekaterina Y. Zaytseva, Mihail I. Mitov, Dana L. Napier, Heidi L. Weiss, B. Mark Evers, Tianyan Gao
Markey Cancer Center Faculty Publications
Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients. Co-culture of adipocytes with colon cancer cells led to a transfer of free fatty acids that released from the adipocytes to …