SREBP-1 in obesity-induced breast cancer: mechanisms and therapeutic perspectives

Breast cancer is the most prevalent form of malignant cancer among women worldwide, and obesity is a significant risk factor. Sterol regulatory element-binding protein 1 (SREBP-1) is a crucial transcription factor that governs lipid synthesis and is aberrantly activated in obesity-induced breast cancer. This review examines the intricate relationship between SREBP-1, obesity, and breast cancer, emphasizing the mechanisms by which obesity-induced activation of SREBP-1 facilitates tumor growth, metastasis, and therapeutic resistance. Obesity disrupts the PI3K/AKT/mTOR and AMPK pathways, resulting in hyperactivation of SREBP-1 and excessive lipid accumulation in breast cancer cells. This metabolic reprogramming fosters a tumor-supportive microenvironment, thereby enhancing cancer cell proliferation, survival, and epithelial-mesenchymal transition. Moreover, obesity adversely affects various breast cancer therapies, including surgery, radiotherapy, chemotherapy, endocrine therapy, and immunotherapy by inducing drug resistance and exacerbating side effects. Targeting SREBP-1 and its regulatory pathways is a promising therapeutic strategy for obesity-induced breast cancer. Natural compounds and small molecules such as fatostatin, mollugin, xanthohumol, and docosahexaenoic acid have demonstrated potential in inhibiting SREBP-1 activation and reducing lipid synthesis in breast cancer cells. Integrating these targeted therapies with conventional treatments may enhance the outcomes of obese patients with breast cancer. Further research is warranted to elucidate the complex mechanisms linking metabolic imbalance and breast cancer, and to develop innovative strategies that effectively combine metabolic and oncological approaches.