ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Int J Biol Sci. 2021 Jul 13;17(12):3048-3058. doi: 10.7150/ijbs.62293. eCollection 2021.

Abstract

Metastasis is a key factor that affects the prognosis of colorectal cancer (CRC), and patients with metastasis have limited treatment options and poor prognoses. EGF, latrophilin, and seven transmembrane domains containing 1 (ELTD1/ADGRL4) are members of the adhesion G protein-coupled receptor (aGPCR) superfamily. In this study, high expression of ELTD1 was correlated with lymph node metastasis and poor outcomes in CRC patients. Both in vitro and in vivo studies showed that ELTD1 markedly promoted the invasion and metastasis of CRC. Moreover, ELTD1 accelerated the transcriptional activity of MMP2, which could rescue the impaired invasiveness of CRC cells caused by the downregulation of ELTD1 expression. In conclusion, our study suggests that ELTD1 might be a potential novel target for the treatment of CRC metastasis.

Keywords: ELTD1; MMP2; colorectal cancer; invasion; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Receptors, G-Protein-Coupled / metabolism*
  • Transcriptional Activation

Substances

  • ADGRL4 protein, human
  • Biomarkers, Tumor
  • Receptors, G-Protein-Coupled
  • MMP2 protein, human
  • Matrix Metalloproteinase 2