Date of Award

5-25-2024

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Supervisor

Lisa Porter

Abstract

Breast cancer is the most prevalent malignancy and the second leading cause of death among Canadian women. Triple negative breast cancer (TNBC) is an aggressive form of breast cancer accounting for 10-20% of breast cancer diagnoses, affecting younger women, and has higher relapse rates than other forms of breast cancer. The tumour microenvironment plays a pivotal role in TNBC progression and metastasis. While much is known about microenvironmental factors in the extracellular matrix, there remains a gap in understanding the role of cell cycle regulators in these processes. Speedy/RINGO is a family of atypical cyclin-like proteins and has emerged as key players in promoting cell cycle progression in breast cancer. Speedy/RINGO can promote progression through cell cycle checkpoints and is elevated in TNBC. This thesis aims to investigate SpdyA and SpdyC family members potential impact on TNBC cell adhesion, migration, and invasion. In vitro studies will use the TNBC cell lines (MDA-MB-231 and MDA-MB-468) to determine the role of SpdyA and SpdyC in mediating metastatic properties of TNBC cells through different cellular substrates and to investigate integrin signaling and MAPK pathway activation. We report for the first time the effects of CRISPR-Cas9 mediated knockout of SpdyA, as well as the influence of overexpression of SpdyA and SpdyC on functional characteristics of TNBC cells. This work aids in the development of better diagnostic markers for metastatic cancer and more personalized therapeutics to treat metastatic breast cancer as well as providing support for targeting Speedy/RINGO as a new therapeutic strategy in TNBC.

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