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Journal of Undergraduate Research

Keywords

autophagy-mediated mechanisms, chemoresistance, cancer

College

Physical and Mathematical Sciences

Department

Chemistry and Biochemistry

Abstract

The resistance of tumor cells to chemotherapy is a critical problem in the clinic and is a common cause of mortality in cancer. Emerging data suggests that resistance to chemotherapy is caused by a tumor-expressed protein called 14-3-3ζ, yet the mechanism to explain 14-3-3ζ-mediated chemoresistance is not completely understood (1). Rapid growing tumors often outgrow their blood supply resulting in regions of hypoxia (low glucose and oxygen). These cells must adapt or die and those that do adapt often become metastatic and chemoresistant. A recently proposed mechanism by which cancer cells are able to adapt to hypoxia is via autophagy, a process in which tumor cells recycle their own components for energy. My research with Dr. Andersen has uncovered a molecular pathway by which 14-3-3ζ promotes autophagy by driving the formation of lipid-enclosed vesicles called autophagosomes, the core cellular structures that recycle cellular contents for energy during periods of hypoxic stress. Specifically, we found that 14-3-3ζ accomplishes this by interacting with a protein called Autophagy related protein 9 (Atg9) which promotes autophagosome formation by delivering golgi-derived membrane to budding autophagosomes. Our data were recently published as the cover story in the December issue of Molecular and Cellular Biology.

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