SECTM1 promotes the development of glioblastoma and mesenchymal transition by regulating the TGFβ1/Smad signaling pathway

Int J Biol Sci. 2024 Jan 1;20(1):78-93. doi: 10.7150/ijbs.84591. eCollection 2024.

Abstract

Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM. Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo. Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFβ1/Smad signaling pathway. Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.

Keywords: EMT; SECTM1; glioblastoma; invasion.

MeSH terms

  • Animals
  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioma* / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Signal Transduction / genetics