Chintalaramulu Naveen, Singh Dhirendra Pratap, Sapkota Biplov, Raman Dayanidhi, Alahari Suresh, Francis Joseph
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Krannert Cardiovascular Research Center, Indiana University Health, Indiana, USA.
Mol Cancer. 2025 Apr 7;24(1):109. doi: 10.1186/s12943-025-02297-8.
Breast cancer (BC) is the most frequently diagnosed cancer in women and the second leading cause of death from cancer among women. Metastasis is the major cause of BC-associated mortality. Accumulating evidence implicates Caveolin-1 (Cav-1), a structural protein of plasma membrane caveolae, in BC metastasis. Cav-1 exhibits a dual role, as both a tumor suppressor and promoter depending on the cellular context and BC subtype. This review highlights the role of Cav-1 in modulating glycolytic metabolism, tumor-stromal interactions, apoptosis, and senescence. Additionally, stromal Cav-1's expression is identified as a potential prognostic marker, offering insights into its contrasting roles in tumor suppression and progression. Furthermore, Cav-1's context-dependent effects are explored in BC subtypes including hormone receptor-positive, HER2-positive, and triple-negative BC (TNBC). The review further delves into the role of Cav-1 in regulating the metastatic cascade including extracellular matrix interactions, cell migration and invasion, and premetastatic niche formation. The later sections discuss the therapeutic targeting of Cav-1 by metabolic inhibitors such as betulinic acid and Cav-1 modulating compounds. While Cav-1 may be a potential biomarker and therapeutic target, its heterogeneous expression and context-specific activity necessitates further research to develop precise interventions. Future studies investigating the mechanistic role of Cav-1 in metastasis may pave the way for effective treatment of metastatic BC.
乳腺癌(BC)是女性中最常被诊断出的癌症,也是女性癌症死亡的第二大主要原因。转移是BC相关死亡的主要原因。越来越多的证据表明,质膜小窝的一种结构蛋白小窝蛋白-1(Cav-1)与BC转移有关。根据细胞环境和BC亚型,Cav-1具有双重作用,既是肿瘤抑制因子又是肿瘤促进因子。本综述重点介绍了Cav-1在调节糖酵解代谢、肿瘤-基质相互作用、细胞凋亡和衰老中的作用。此外,基质Cav-1的表达被确定为一种潜在的预后标志物,为其在肿瘤抑制和进展中的不同作用提供了见解。此外,还在包括激素受体阳性、HER2阳性和三阴性乳腺癌(TNBC)在内的BC亚型中探讨了Cav-1的背景依赖性效应。该综述进一步深入研究了Cav-1在调节转移级联反应中的作用,包括细胞外基质相互作用、细胞迁移和侵袭以及转移前生态位的形成。后面的章节讨论了通过桦木酸等代谢抑制剂和Cav-1调节化合物对Cav-1进行治疗靶向。虽然Cav-1可能是一种潜在的生物标志物和治疗靶点,但其异质性表达和背景特异性活性需要进一步研究以开发精确的干预措施。未来研究Cav-1在转移中的机制作用可能为转移性BC的有效治疗铺平道路。