Caveolin-1-deficient fibroblasts promote migration, invasion, and stemness via activating the TGF-β/Smad signaling pathway in breast cancer cells

• Published in: Acta biochimica et biophysica Sinica Vol. 54; no. 11; pp. 1587 - 1598
• Main Authors: Huang, Qingyun, Wu, Longyuan, Wang, Yi, Kong, Xinyu, Xiao, Xinhua, Huang, Qiyuan, Li, Miao, Zhai, Yujia, Shi, Fuxiu, Zhao, Ruichen, Zhong, Junpei, Xiong, Lixia
• Format: Journal Article
• Language: English
• Published: China China Science Publishing & Media Ltd 01.11.2022
• Subjects: breast neoplasms; Breast Neoplasms - metabolism; cancer-associated fibroblasts; caveolin 1; Caveolin 1 - genetics; Caveolin 1 - metabolism; Cell Line, Tumor; Cell Movement; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Female; Fibroblasts - metabolism; Humans; Signal Transduction; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta1 - metabolism; transforming growth factor-β; Tumor Microenvironment; cancer-associated fibroblasts; caveolin 1; epithelial-mesenchymal transition; transforming growth factor-β; breast neoplasms
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.3724/abbs.2022150

Cancer-associated fibroblasts (CAFs) represent one of the main components in the tumor stroma and play a key role in breast cancer progression. Transforming growth factor-β (TGF-β) has been established to mediate breast cancer metastasis by regulating the epithelial-mesenchymal transition (EMT) and stemness of cancer cells. Caveolin-1 (CAV-1) is a scaffold protein of caveolae that is related to the proliferation and metabolism of cancer cells. It is now well demonstrated that CAV-1 deficiency in the tumor stroma is positively correlated with distant metastasis, but the mechanism remains unclear. Here, we explore whether CAV-1-deficient fibroblasts play an essential role in the EMT and stemness of breast cancer cells (BCCs) through TGF-β signaling. We establish a specific small interfering RNA (siRNA) to inhibit CAV-1 expression in fibroblasts and coculture them with BCCs to investigate the effect of CAV‑1-deficient fibroblasts and the tumor microenvironment on breast cancer progression. This study refreshingly points out that CAV-1 deficiency in fibroblasts enhances TGF-β1 secretion and then activates the TGF-β1/Smad signaling pathway of BCCs, thus promoting the metastasis and stemness of BCCs. Collectively, our findings indicate an unexpected role of CAV-1 deficiency in fibroblasts and the tumor microenvironment as a permissive factor, which is regulated by the TGF-β1 signaling pathway in BCCs.