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

作　　者：Qingyun Huang Longyuan Wu Yi Wang Xinyu Kong Xinhua Xiao Qiyuan Huang Miao Li Yujia Zhai Fuxiu Shi Ruichen Zhao Junpei Zhong Lixia Xiong 

机构地区：[1]Department of Pathophysiology,Medical College,Nanchang University,Nanchang 330006,China [2]The First Affiliated Hospital,Nanchang University,Nanchang 330006,China [3]Key Laboratory of Functional and Clinical Translational Medicine,Fujian Province University,Xiamen 361023,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第11期1587-1598,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.31860317 and 32160169);the Key Project of Jiangxi Provincial Natural Science Foundation(No.20212ACB206040);the National Natural Science Foundation of Jiangxi Province(No.20202BAB206056);the postgraduate innovation special fund project of Nanchang University(No.YC2020-S049);the Key Laboratory of Functional and Clinical Translational Medicine,Fujian Province University(No.XMMCFCTM202103);the college students innovation training program of Nanchang University(Nos.202110403005,S202010403034,2021CX142 and 2020CX263).

摘　　要：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-βsignaling.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.

关 键 词：caveolin 1 cancer-associated fibroblasts breast neoplasms epithelial-mesenchymal transition transforming growth factor-β 

分 类 号：R737.9[医药卫生—肿瘤]