Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Trevor Shepherd

Abstract

NUAK1, a downstream substrate of the stress metabolism regulator Liver kinase B1 (LKB1), has been implicated as an oncogene and tumor suppressor, with distinct roles in cell cycle, senescence and cell adhesion. Epithelial ovarian cancer (EOC) spheroids remain dormant during intraperitoneal metastasis with reduced proliferation and metabolism to survive metabolically harsh conditions, possibly implicating a role of NUAK1 in EOC spheroid biology. I hypothesize that NUAK1 is regulated by LKB1 to promote dormancy in EOC. I demonstrate that NUAK1 expression and phosphorylation is regulated by LKB1 in EOC cell lines. NUAK1 is largely under-expressed in many established and new ascites-derived EOC cell lines; in fact, further NUAK1 knockdown increases spheroid cell viability, size, and reattachment capability. Pharmacologic NUAK1/2 inhibition increased EOC cell growth and clonogenicity. Collectively, my data supports NUAK1 as having tumour suppressive activity downstream of LKB1 in EOC.

Available for download on Thursday, June 21, 2018

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