Tiwari Urvashi, Akhtar Salman, Mir Snober S, Khan Mohammad Kalim Ahmad
Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, 226026, India.
Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, 226026, India.
Mol Biol Rep. 2025 Jul 1;52(1):663. doi: 10.1007/s11033-025-10775-x.
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.
乳腺癌是全球女性中最常见的恶性肿瘤形式，肥胖是一个重要的风险因素。固醇调节元件结合蛋白1（SREBP-1）是一种关键的转录因子，它控制脂质合成，并且在肥胖诱导的乳腺癌中异常激活。本综述探讨了SREBP-1、肥胖和乳腺癌之间的复杂关系，强调了肥胖诱导的SREBP-1激活促进肿瘤生长、转移和治疗耐药性的机制。肥胖会破坏PI3K/AKT/mTOR和AMPK信号通路，导致SREBP-1过度激活以及乳腺癌细胞中脂质过度积累。这种代谢重编程促进了肿瘤支持性微环境的形成，从而增强癌细胞的增殖、存活和上皮-间质转化。此外，肥胖对各种乳腺癌治疗产生不利影响，包括手术、放疗、化疗、内分泌治疗和免疫治疗，通过诱导耐药性和加剧副作用。靶向SREBP-1及其调节通路是肥胖诱导的乳腺癌的一种有前景的治疗策略。天然化合物和小分子如法托他汀、软紫草素、黄腐酚和二十二碳六烯酸已显示出抑制SREBP-1激活和减少乳腺癌细胞中脂质合成的潜力。将这些靶向治疗与传统治疗相结合可能会改善肥胖乳腺癌患者的治疗效果。有必要进一步研究以阐明代谢失衡与乳腺癌之间的复杂机制，并开发有效结合代谢和肿瘤学方法的创新策略。
