Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2021; 13(9): 980-994
Published online Sep 15, 2021. doi: 10.4251/wjgo.v13.i9.980
Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression
Motomichi Fujita, Hideo Suzuki, Fumio Fukai
Motomichi Fujita, Fumio Fukai, Department of Molecular Patho-Physiology, Tokyo University of Science, Noda 278-8510, Chiba, Japan
Hideo Suzuki, Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
Author contributions: All authors contributed equally to the conception of this study, drafting, critical revision, and editing of the manuscript, and final approval of the submission.
Conflict-of-interest statement: The authors declare no conflicts of interests in regards to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Fumio Fukai, PhD, Professor, Department of Molecular Patho-Physiology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Chiba, Japan.
Received: February 21, 2021
Peer-review started: February 21, 2021
First decision: May 8, 2021
Revised: June 3, 2021
Accepted: August 11, 2021
Article in press: August 11, 2021
Published online: September 15, 2021

Tenascin-C (TNC) is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies, including colon cancer. Although TNC is considered a negative prognostic factor for cancer patients, the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood. We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site, termed TNIIIA2, can potently and persistently activate beta1-integrins. In contrast, the peptide FNIII14, which contains a cryptic bioactive site within the fibronectin molecule, can inactivate beta1-integrins. This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer, particularly the major involvement of its cryptic functional site TNIIIA2. We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

Keywords: Tenascin-C, TNIIIA2, Beta1-integrin, Integrin activation, Colitis-associated colorectal cancer, Colon cancer

Core Tip: Exposure of the cryptic functional site TNIIIA2 from the Tenascin-C (TNC) molecule and its potent and sustained activation of beta1-integrins appear to be associated with the development of colon cancer and its malignant progression. Inhibition of the biological function of TNIIIA2 derived from TNC molecule may be a promising strategy for the prevention and treatment of colon cancer.