Sphingomyelin synthase 1 regulates the epithelial‑to‑mesenchymal transition mediated by the TGF‑β/Smad pathway in MDA‑MB‑231 cells

Abstract

Breast cancer is the most common cancer in women and a leading cause of cancer-associated mortalities in the world. Epithelial-to-mesenchymal transition (EMT) serves an important role in the process of metastasis and invasive ability in cancer cells, and transforming growth factor β1 (TGF-β1) have been investigated for promoting EMT. However, in the present study, the role of the sphingomyelin synthase 1 (SMS1) in TGF-β1-induced EMT development was investigated. Firstly, bioinformatics analysis demonstrated that the overexpression of SMS1 negatively regulated the TGFβ receptor I (TβRI) level of expression. Subsequently, the expression of SMS1 was decreased, whereas, SMS2 had no significant difference when MDA-MB-231 cells were treated by TGF-β1 for 72 h. Furthermore, the present study constructed an overexpression cells model of SMS1 and these cells were treated by TGF-β1. These results demonstrated that overexpression of SMS1 inhibited TGF-β1-induced EMT and the migration and invasion of MDA-MB-231 cells, increasing the expression of E-cadherin while decreasing the expression of vimentin. Furthermore, the present study further confirmed that SMS1 overexpression could decrease TβRI expression levels and blocked smad family member 2 phosphorylation. Overall, the present results suggested that SMS1 could inhibit EMT and the migration and invasion of MDA-MB-231 cells via TGF-β/Smad signaling pathway.

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

“…EMT plays a vital role in tumor metastasis as is evident by the upregulated expression of N-cadherin and Vimentin, while the expression level of E-cadherin is downregulated (34). TGF-β/Smad signaling pathway is an important driver in promoting the EMT process via activating the canonical pathway as with Smad family members or non-canonical signaling molecules such as Rho kinase (35,36). TGF-β1-induced EMT has been implicated in diabetic kidney diseases, fibrosis phenotype and tumor cell Following serum starvation for 24 h, stable NRP1-silenced A549 and H226 cells were treated with or without TGF-β1 (5 ng/ml) for 48 h. The expression of p-Smad3, Smad3, Snail, MMP2, MMP9, N-cadherin, Vimentin was analyzed by western blot analysis.…”

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

“…In contrast, the overexpression of SMS1-inhibited EMT induced by TGFβ1 and coincides with the upregulation of E-cadherin and downregulation of vimentin [155]. Another study indicated that SMS1 blocks EMT via repressing the expression of TGFβR1 and SMAD2 phosphorylation [155]. Overall, these findings imply that sphingolipids play important roles in EMT induced by TGFβ, and a deeper understanding of the mechanisms by which sphingolipids regulate cancer cell signaling and metastasis will be beneficial to improve cancer treatment.…”

“…The decreased expression of SMS1 was found during TGFβ1induced EMT in the MDA-MB-231 cell line. In contrast, the overexpression of SMS1-inhibited EMT induced by TGFβ1 and coincides with the upregulation of E-cadherin and downregulation of vimentin [155]. Another study indicated that SMS1 blocks EMT via repressing the expression of TGFβR1 and SMAD2 phosphorylation [155].…”

Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

“…EMT plays a vital role in tumor metastasis, accompanied by the up-regulated expression of N-cadherin and Vimentin, meanwhile the expression level of E-cadherin is down-regulated [31]. TGFβ/Smad signaling pathway is an important driver in promoting EMT process via activating canonical pathway like Smad family members or non-canonical signaling molecules like Rho kinase [32,33]. TGF-β1induced EMT has been implicated in diabetic kidney diseases, fibrosis phenotype and tumor cell metastasis [34][35][36].…”