GALNT6 Promoted Breast Cancer Metastasis by Regulating EMT via TGF-β/Smad Signaling Pathway

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.