Suppression of epithelial to mesenchymal transition by Nidogen-1 through regulation of vimentin and TGF-β/β-catenin signaling in triple-negative breast cancer

Abstract

Nidogen-1 (NID1) is a secreted protein and a type of basement membrane glycoprotein. NID1 is known to regulate migration and metastasis of various cancer cells including ovarian and breast cancer cells. However, the role of NID1 and its mechanism in Triple-negative breast cancer (TNBC) has been hardly known. To investigate the role of NID1 in TNBC, I generated stable NID1-overexpressing TNBC cells. I found that overexpression of NID1 decreased cell proliferation, migration, and invasion. I also found that NID1 negatively regulated vimentin protein level via the ubiquitin-proteasome degradation pathway. Furthermore, TGF-β/Smad2 signaling and nuclear activation of β-catenin signaling were inhibited by NID1 overexpression, leading to suppression of cell migration and epithelial to mesenchymal transition (EMT). Accordingly, the expression of vimentin and cell migration were reduced by treatment with recombinant NID1 and conditioned medium from NID1-overexpressing cells. Together, I suggest that NID1 may act as a tumor suppressor and represent a valuable therapeutic option for TNBC treatment.