INVESTIGATING THE ROLE OF FATTY ACID SYNTHASE (FASN) IN ADIPOGENESIS AND OBESITY-RELATED BREAST CANCER PROGRESSION USING CELLULAR AND MOLECULAR APPROACHES

Abstract

During the last few decades, the prevalence of obesity has rapidly increased, affecting a significant portion of the population. Obesity, characterized by a high body mass index (BMI) and excessive fat mass, is a considerable risk factor for the onset, progression, and poor prognosis of various neoplasms, including breast carcinoma. Fatty acid synthase (FASN), a critical enzyme responsible for de novo lipogenesis, is notably overexpressed in breast cancer tissues and adipose tissue of obese individuals. This overexpression suggests a potential mechanistic link between obesity and breast tumor development. In the present study, we sought to investigate the importance of FASN in adipocyte-mediated breast cancer cell pathogenesis by applying an indirect co-culture method that uses a conditioned medium generated from 3T3-L1 mature adipocytes. Our findings confirmed that FASN is essential in modulating the adipogenic features of 3T3-L1 adipocytes and contributes to the tumor-promoting behavior of malignant breast cancer. Furthermore, we illustrated that breast carcinoma cells’ migration and proliferation abilities were enhanced when A-CM was applied to the cells. The enhancement in migration and proliferation was coupled with increased expression of FASN in the breast tumor cells. Notably, inhibition of FASN enzyme activity in adipocytes led to reduced FASN expression in breast cancer cells, accompanied by a marked decrease in their migratory and proliferative abilities. These findings highlight the significance of FASN in mediating adipocyte-induced breast cancer progression, suggesting the candidacy of FASN as a potential pharmacological target for obesity-induced breast carcinoma. However, further in vitro and in vivo studies are necessary to elucidate the detailed molecular mechanisms by which FASN drives the interplay between obesity and breast cancer.

Date of Award	2024
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences