Master of Science
Anatomy and Cell Biology
Shepherd, Trevor G.
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.
Laski, Jeremi, "AMPK Signalling As A Regulator Of Autophagy In A Model Of Ovarian Tumour Dormancy" (2019). Electronic Thesis and Dissertation Repository. 6229.
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Available for download on Tuesday, December 31, 2019