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Sphingomyelin synthase 1 regulates the epithelial?to?mesenchymal transition mediated by the TGF??/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 ?1 (TGF??1) have been investigated for promoting EMT. However, in the present study, the role of the sphingomyelin synthase 1 (SMS1) in TGF??1?induced EMT development was investigated. Firstly, bioinformatics analysis demonstrated that the overexpression of SMS1 negatively regulated the TGF? receptor I (T?RI) 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??1 for 72 h. Furthermore, the present study constructed an overexpression cells model of SMS1 and these cells were treated by TGF??1. These results demonstrated that overexpression of SMS1 inhibited TGF??1?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 T?RI 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??/Smad signaling pathway.

SUBMITTER: Liu S

PROVIDER: S-EPMC6323219 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Liu Shuang S Hou Huan H Zhang Panpan P Wu Yifan Y He Xuanhong X Li Hua H Yan Nianlong N

Molecular medicine reports 20181204 2

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 ...[more]

PMID: 30535436

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Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. Parental MDA-MB-231 cells and MDA-MB-231(SA) cells were cultured in cell culture flasks. RNA was isolated in order to compare the gene expression profiles of these cell variants. Total of two samples. No replicates.

Dataset Information

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

Publications

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

Similar Datasets

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