摘要
该文研究了N-乙酰半乳糖氨基转移酶6(GALNT6)对乳腺癌上皮–间充质转化(EMT)的影响及其机制。乳腺癌细胞中GALNT6表达被敲低后,间充质标志物E-cadherin表达增加,N-cadherin、Vimentin等表达减少。同时,通过恢复shGALNT6细胞中GALNT6的表达,可以提高间充质标志物的表达。转化生长因子(transforming growth factor,TGF)处理乳腺癌细胞时,Vimentin表达升高,E-cadherin表达降低。然而,在GALNT6敲低细胞中却得到相反的结果。当使用Smad3的抑制剂SIS3处理时,EMT标记物的表达不受GALNT6敲低的影响,说明GALNT6主要通过Smad途径诱导EMT。此外,Smad3和TGFBR2可被GALNT6糖基化。研究结果表明,GALNT6通过TGF/Smad信号通路诱导EMT促进乳腺癌转移,这提示了其在乳腺癌预后和治疗中的潜在作用。
This study investigated the effects of GALNT6 on EMT (epithelial-mesenchymal transition) in breast cancer and the underlying mechanism.Results showed that knockdown of GALNT6 in breast cancer cells increased the expression of E-cadherin,and decreased the expression of mesenchymal markers,including N-cadherin and Vimentin.Meanwhile,the expression of mesenchymal markers was increased by restoring the expression of GALNT6 in shGALNT6 cells.When the breast cancer cells were treated with TGF-β1 (transforming growth factor β1),the expression of Vimentin was increased while the expression of E-cadherin was decreased.However,the opposite results were obtained in GALNT6 knockdown cells.While treated with SIS3,an inhibitor of Smad3,the expression of EMT markers were not affected by knockdown of GALNT6,indicating that GALNT6 induced EMT mainly via the Smad pathway.Furthermore,Smad3 and TGFBR2 are glycosylated by GALNT6.Collectively,the findings suggested that GALNT6 induced EMT to promote breast cancer metastasis via TGF-β/Smad signaling pathway,supporting its prognostic and therapeutic utility in breast cancer.
作者
张一宁
陈吕奥
吴亚敏
张月
姚恩泽
陈晓明
ZHANG Yining;CHEN Lüao;WU Yamin;ZHANG Yue;YAO Enze;CHEN Xiaoming(School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2021年第4期759-769,共11页
Chinese Journal of Cell Biology
基金
supported by the National Natural Science Foundation of China (Grant No.31570805)
Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A)
Scientific and Technological Innovation Activity Plan of College Students in Zhejiang Province (the Xinmiao Talent Program)(Grant No.2019R413081)。
