Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Shepherd, Trevor G.

Abstract

One of the hallmarks of epithelial ovarian cancer (EOC) metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into 3D structures. Previous literature suggests that as EOC cells form spheroids they undergo bioenergetic stress, activate AMP-activated protein kinase (AMPK) signaling, and thereby force cells to enter a metabolically quiescent state. We have previously shown that EOC spheroids up- regulate autophagy, a process that provides energy during starvation conditions. Herein, I examined the role of AMPK-mediated signaling regulation of autophagy in a model of ovarian tumour dormancy. Attenuation of AMPK signaling in EOC spheroids resulted in reduction of autophagic flux in all EOC lines although this reduction may occur in an LC3 and p62 independent manner. Interestingly, I identified that AMPK activation in spheroids is likely regulated by CAMKK-beta. The results of this study help further our understanding of the complex mechanisms driving autophagy in late-stage ovarian cancer.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Tuesday, December 31, 2019

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