Research Paper Volume 11, Issue 19 pp 8526—8541
Ninjurin 2 overexpression promotes human colorectal cancer cell growth in vitro and in vivo
- 1 Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2 Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China
- 3 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 4 Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Received: August 16, 2019 Accepted: September 22, 2019 Published: October 9, 2019
https://doi.org/10.18632/aging.102336How to Cite
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.
Abbreviations
CRC: Colorectal cancer; Co-IP: co-immunoprecipitation; FBS: fetal bovine serum; FACS: fluorescent-activated cell sorting; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; IHC: immunohistochemistry; NINJ1: Ninjurin 1; NINJ2: Ninjurin 2; PI: propidium iodide; OD: optical density; SCID: severe combined immunodeficient; sgRNA: small guide RNA; shRNA: short hairpin RNA; SD: standard deviation; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling.