Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

Harjot Athwal; Arpitha Kochiyanil; Vasudeva Bhat; Alison L Allan; Armen Parsyan

doi:10.3389/fonc.2024.1370565

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

Front Oncol. 2024 Mar 28:14:1370565. doi: 10.3389/fonc.2024.1370565. eCollection 2024.

Authors

Harjot Athwal¹, Arpitha Kochiyanil², Vasudeva Bhat^{1

3}, Alison L Allan^{1

3

4}, Armen Parsyan^{1

3

4

5

6}

Affiliations

¹ Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
² Faculty of Science, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ London Regional Cancer Program, London Health Sciences Centre, Lawson Health Research Institute, London, ON, Canada.
⁴ Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁵ Division of General Surgery, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁶ Department of Surgery, St. Joseph's Health Care London and London Health Sciences Centre, London, ON, Canada.

Abstract

Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies. Centrosomes and their associated proteins have been shown to play key roles in the pathogenesis of breast cancer and thus represent promising targets for drug and biomarker development. Centrosomes are fundamental cellular structures in the mammalian cell that are responsible for error-free execution of cell division. Centrosome amplification and aberrant expression of its associated proteins such as Polo-like kinases (PLKs), Aurora kinases (AURKs) and Cyclin-dependent kinases (CDKs) have been observed in various cancers, including breast cancer. These aberrations in breast cancer are thought to cause improper chromosomal segregation during mitosis, leading to chromosomal instability and uncontrolled cell division, allowing cancer cells to acquire new genetic changes that result in evasion of cell death and the promotion of tumor formation. Various chemical compounds developed against PLKs and AURKs have shown meaningful antitumorigenic effects in breast cancer cells in vitro and in vivo. The mechanism of action of these inhibitors is likely related to exacerbation of numerical genomic instability, such as aneuploidy or polyploidy. Furthermore, growing evidence demonstrates enhanced antitumorigenic effects when inhibitors specific to centrosome-associated proteins are used in combination with either radiation or chemotherapy drugs in breast cancer. This review focuses on the current knowledge regarding the roles of centrosome and centrosome-associated proteins in breast cancer pathogenesis and their utility as novel targets for breast cancer treatment.

Keywords: AURK; CDK; CEP; CHK1/WEE1; PLK; breast cancer; centriole; centrosome.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. AP lab research is supported by the Grant 942549 from the Cancer Research Society (CRS) and Canadian Institutes of Health Research (CIHR, Funding Reference Number 184668)/Institute of Cancer Research (ICR), Operating Grants 2022 Competition, Targeted Funding Opportunity, and by the Opportunities Fund of the Academic Health Sciences Centre Alternative Funding Plan of the Academic Medical Organization of Southwestern Ontario (AMOSO, Project #F20-007). AP is also supported by the Clinical Scientist Award, Department of Surgery, Western University. AA’s breast cancer research is supported by a Project Grant from the Canadian Institutes of Health Research (CIHR; # PJT-75100). AA, VB and HA are supported by Breast Cancer Canada.