LAMA5 promotes cell proliferation and migration in ovarian cancer by activating Notch signaling pathway

FASEB J. 2023 Sep;37(9):e23109. doi: 10.1096/fj.202300306R.

Abstract

LAMA5 (laminin α5) is a member of the laminin family. Despite the recent research implicating LAMA5 in cancer, the function of LAMA5 has remained uncertain in the progression of ovarian cancer (OC). Here, we investigated the functional influences of LAMA5 knockdown on OC in vitro and in vivo. In this study, we used immunohistochemistry (IHC) analysis to detect the relative expression of LAMA5 in OC and non-cancer tissues, and we analyzed its connection with the overall survival (OS) of OC patients. To prove the role of LAMA5 in cell proliferation, migration, and invasion, LAMA5 expression in OC cell lines was inhibited by lentivirus. Compared with normal fallopian tube tissue, epithelial ovarian cancer (EOC) tissue showed critically higher LAMA5 expression levels; additionally, high LAMA5 levels were a poor predictor of OS. We found that cell progression was restrained in LAMA5-knockdown OC cell lines in vivo and in vitro. Finally, LAMA5 might be a commanding inducer of the expression of epithelial-mesenchymal transition (EMT) and Notch signaling pathway-related markers. Together, our research indicates that LAMA5 is highly connected to OC progression as it may play a role in the EMT process through the Notch signaling pathway.

Keywords: LAMA5; Notch signaling pathway; cell migration; cell proliferation; epithelial-mesenchymal transition (EMT); ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Signal Transduction