The EMT-related transcription factor snail up-regulates FAPα in malignant melanoma cells

Exp Cell Res. 2018 Mar 15;364(2):160-167. doi: 10.1016/j.yexcr.2018.01.039. Epub 2018 Feb 2.

Abstract

FAPα is a cell surface serine protease, mainly expressed in tumor stromal fibroblasts in more than 90% of human epithelial carcinomas. Due to its almost no expression in normal tissues and its tumor-promoting effects, FAPα has been studied as a novel potential target for antitumor therapy. However, the regulation mechanism on FAPα expression is poorly understood. In this study, we found that overexpression of snail significantly increased the mRNA and protein expression levels of FAPα in malignant melanoma B16 and SK-MEL-28 cells. Overexpression of snail increased FAPα promoter activity remarkably. Snail could directly bind to FAPα promoter to regulate FAPα expression. Moreover, snail expression was positively correlated to FAPα expression in human cutaneous malignant melanoma. Furthermore, knockdown of FAPα markedly reduced snail-induced cell migration. Overall, our findings provide a novel regulation mechanism on FAPα expression and highlight the role of snail/FAPα axis as a novel target for melanoma treatment.

Keywords: FAPα; Malignant melanoma; Regulation mechanism; Snail.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endopeptidases
  • Gelatinases / genetics
  • Gelatinases / metabolism*
  • Humans
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Membrane Proteins
  • Snail Family Transcription Factors
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases