Semaphorin 3c (SEMA3C) as a potential therapeutic target in breast cancer
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Bhasin, Satyam
issued: 2024-03-27T21:47:10Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Breast cancer (BCa) is a significant cause of cancer-related deaths among females globally. Approximately 45% of BCa patients develop treatment resistance or suffer from a lack of targeted therapies. Previously, we have shown that Semaphorin 3C (SEMA3C) is an autocrine growth factor that drives the growth and treatment resistance of various cancers. This study aims to investigate the functional role of SEMA3C in breast cancer progression and treatment resistance. My analysis of clinical datasets revealed elevated levels of SEMA3C mRNA in breast tumors compared to normal adjacent tissue. SEMA3C expression was positively correlated with the expression of various oncogenes implicated in breast cancer. Both estrogen receptor (ER) positive (ER⁺/HER2ˉ) BCa and triple negative breast cancer (TNBC) cells exhibited higher levels of SEMA3C protein compared to a non-cancer mammary epithelial cell line (MCF10A). Stimulation with recombinant SEMA3C activated EGFR, MAPK and AKT signaling in both ER⁺ and TNBC cells. Conversely, SEMA3C silencing inhibited ER expression, EGFR, MAPK, and AKT signaling, while inducing apoptosis. Silencing of SEMA3C significantly suppressed the growth of ER⁺ BCa and TNBC cells, indicating a growth dependency on SEMA3C. Tamoxifen-resistant cells (TamC3, TamR3) remained reliant on SEMA3C for growth and survival, suggesting its persistence in treatment resistance. Additionally, SEMA3C suppression enhanced the efficacy of certain chemotherapies and targeted therapies in TNBC cells. Additionally, treatment with SEMA3C pathway inhibitors, B1SP (Fc fusion protein) and ALS, attenuated SEMA3C-induced signaling and growth in both ER⁺ and TNBC cells. This study highlights the functional role of SEMA3C in breast cancer signaling and growth, suggesting its potential as a therapeutic target. Targeting SEMA3C may offer benefits in improving treatment outcomes for breast cancer patients, particularly in cases of endocrine treatment resistance and TNBC.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87643
note: SEMAPHORIN 3C (SEMA3C) AS A POTENTAL THERAPEUTIC TARGET IN BREAST CANCER by Satyam Bhasin B. Tech, NIIT University, 2017 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Interdisciplinary Oncology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) March 2024 © Satyam Bhasin, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Semaphorin 3C (SEMA3C) as a potential therapeutic target in breast cancer submitted by Satyam Bhasin in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Interdisciplinary Oncology Examining Committee: Christopher J Ong, Associate Professor, Department of Urologic Sciences, UBC Supervisor Yuzhuo Wang, Professor, Department of Urologic Sciences, UBC Supervisory Committee Member Wan Lam, Professor, Department of Pathology and Laboratory Medicine, UBC University Examiner Chinten James Lim, Associate Professor, Department of Pediatrics, UBC University Examiner Additional Supervisory Committee Members: Artem Cherkasov, Professor, Department of Urologic Sciences, UBC Co-Supervisor Christopher Maxwell, Associate Professor, Department of Pediatrics, UBC Supervisory Committee Member iii Abstract Breast cancer (BCa) is a significant cause of cancer-related deaths among females globally. Approximately 45% of BCa patients develop treatment resistance or suffer from a lack of targeted therapies. Previously, we have shown that Semaphorin 3C (SEMA3C) is an autocrine growth factor that drives the growth and treatment resistance of various cancers. This study aims to investigate the functional role of SEMA3C in breast cancer progression and treatment resistance. My analysis of clinical datasets revealed elevated levels of SEMA3C mRNA in breast tumors compared to normal adjacent tissue. SEMA3C expression was posit…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0440945
language: eng
degree discipline: Interdisciplinary Oncology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Ong, Christopher J.
contributor: Cherkasov, Artem
type: Text
identifier URI: http://hdl.handle.net/2429/87643