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Research Paper|Volume 11, Issue 19|pp 8526—8541

Ninjurin 2 overexpression promotes human colorectal cancer cell growth in vitro and in vivo

Gang Li1, Li-Na Zhou2, Han Yang1, Xixi He3, Yuxia Duan4, Fang Wu3
  • 1Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 2Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
  • 3Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 4Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
* Co-first authors
Received: August 16, 2019Accepted: September 22, 2019Published: October 9, 2019
https://doi.org/10.18632/aging.102336

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ninjurin 2 (NINJ2) is a novel adhesion molecule. Its expression and potential function in human colorectal cancer (CRC) cells are studied. We show that NINJ2 is overexpressed in established (HT-29) and primary CRC cells and in human colon cancer tissues. Its expression level is low in colon epithelial cells and normal colon tissues. NINJ2 shRNA or knockout (by CRSIPR/Cas9) potently inhibited human CRC cell survival and proliferation, while significantly inducing cell apoptosis. Conversely, lentivirus-mediated NINJ2 overexpression promoted CRC cell proliferation. NINJ2 co-immunoprecipitated with multiple RTKs (EGFR, PDGFRα/β and FGFR) in CRC cells and human colon cancer tissues. In HT-29 cells, RTKs’ downstream signalings, Akt and Erk, were significantly inhibited by NINJ2 shRNA or knockout, but augmented following ectopic NINJ2 overexpression. In vivo, NINJ2-silenced or NINJ2-knockout CRC xenografts grew significantly slower than the control xenografts. Akt-Erk activation was largely inhibited in CRC xenografts with NINJ2 silencing or knockout. Taken together, NINJ2 overexpression promotes CRC cell growth in vitro and in vivo.