Jiang Xingshan, Xiong Yiqin, Yu Jianyu, Avellino Anthony, Liu Shanshan, Han Xiaochun, Wang Zhaohua, Shilyansky Jonathan S, Curry Melissa A, Hao Jiaqing, Sauter Edward R, Huang Yi, Sugg Sonia L, Li Bing
Department of Pathology, University of Iowa, 431 Newton Road, Iowa City, IA, 52242, USA.
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
Discov Oncol. 2025 Mar 19;16(1):357. doi: 10.1007/s12672-025-02117-x.
The incidence of breast cancer continues to rise each year despite significant advances in diagnosis and treatment. Obesity-associated dysregulated lipid metabolism is believed to contribute to the increasing risk of breast cancer. However, the mechanisms linking lipid dysregulation to breast cancer risk and progression remain to be determined. The family of fatty acid binding proteins (FABPs) evolves to facilitate lipid transport and metabolism. As the predominant isoforms of FABP members expressed in breast tissue, adipose FABP (A-FABP, also known as FABP4) and epithelial FABP (E-FABP, FABP5) have been shown to play critical roles in breast carcinogenesis. In this study, we collected surgical breast tissue samples from 96 women with different subtypes of breast cancer and comprehensively analyzed the expression pattens of FABP4 and FABP5. We found that distinct expression profiles of FABP4 and FABP5 were associated with their unique roles in breast cancer development. FABP4, mainly expressed in breast stroma, especially in adipose tissue, likely supported neighboring tumor cell lymphovascular invasion through secretion from adipocytes. In contrast, FABP5, primarily expressed in epithelial-derived tumor cells, could promote tumor metastasis by enhancing lipid metabolism. Thus, elevated levels of FABP4 and FABP5 may serve as poor prognostic markers for breast cancer. Inhibiting the activity of FABP4 and/or FABP5 may offer a novel strategy for breast cancer therapy.
尽管在乳腺癌的诊断和治疗方面取得了重大进展，但乳腺癌的发病率仍逐年上升。肥胖相关的脂质代谢失调被认为会增加患乳腺癌的风险。然而，脂质失调与乳腺癌风险及进展之间的联系机制仍有待确定。脂肪酸结合蛋白（FABP）家族的进化是为了促进脂质的运输和代谢。作为在乳腺组织中表达的FABP成员的主要亚型，脂肪型FABP（A-FABP，也称为FABP4）和上皮型FABP（E-FABP，FABP5）已被证明在乳腺癌发生过程中起关键作用。在本研究中，我们收集了96例不同亚型乳腺癌女性患者的手术乳腺组织样本，并全面分析了FABP4和FABP5的表达模式。我们发现，FABP4和FABP5不同的表达谱与其在乳腺癌发展中的独特作用相关。FABP4主要表达于乳腺基质，尤其是脂肪组织中，可能通过脂肪细胞分泌来支持邻近肿瘤细胞的淋巴管浸润。相反，FABP5主要表达于上皮来源的肿瘤细胞中，可通过增强脂质代谢促进肿瘤转移。因此，FABP4和FABP5水平升高可能是乳腺癌预后不良的标志物。抑制FABP4和/或FABP5的活性可能为乳腺癌治疗提供一种新策略。
