Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor(s)

Dr. Moshmi Bhattacharya

Abstract

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is a leading cause of mortality in these patients. Fibulin-3, a secreted extracellular matrix protein, has a pro-invasive role in other cancers. However, a role for fibulin-3 in TNBC invasion is unknown. We have previously shown that KISS1R signaling promotes TNBC cell invasion through EGFR and MMP-9 activity, via β-arrestin2. Thus, we hypothesized that KISS1R signaling promotes TNBC cell invasion via fibulin-3. Our clinical data suggests that plasma fibulin-3 levels are elevated in metastatic TNBC patients. Additionally, we found that invasive breast cancer cells have increased expression of fibulin-3 and treatment with kisspeptin, the KISS1R ligand, further increased fibulin-3 expression and secretion. Also, depletion of β-arrestins in TNBC cells decreased fibulin-3 expression. Furthermore, fibulin-3 depletion in TNBC cells inhibited cell invasiveness through decreased MMP-9 activity. These results identify fibulin-3 as a new signaling partner of KISS1R and as a potential anti-metastasis target in TNBC.

Available for download on Saturday, August 17, 2019


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