e-Article
Cancer‐associated fibroblast migration in non‐small cell lung cancers is modulated by increased integrin α11 expression
Document Type
Academic Journal
Author
Iwai, Moe; Tulafu, Miniwan; Togo, Shinsaku; Kawaji, Hideya; Kadoya, Kotaro; Namba, Yukiko; Jin, Jin; Watanabe, Junko; Okabe, Takahiro; Hidayat, Moulid; Sumiyoshi, Issei; Itoh, Masayoshi; Koyama, Yu; Ito, Yasuhiko; Orimo, Akira; Takamochi, Kazuya; Oh, Shiaki; Suzuki, Kenji; Hayashizaki, Yoshihide; Yoshida, Koji; Takahashi, Kazuhisa
Source
Molecular Oncology. May 2021, Vol. 15 Issue 5, p1507, 21 p.
Subject
Language
English
ISSN
1574-7891
Abstract
Abbreviations Introduction Cancer‐associated fibroblasts (CAFs) constitute the key cellular components of cancer stroma in many solid cancer types and contain heterogeneous subpopulations that have distinct phenotypes and functions [1]. CAFs [...]
Cancer‐associated fibroblasts (CAFs) regulate cancer progression through the modulation of extracellular matrix (ECM) and cancer cell adhesion. While undergoing a series of phenotypic changes, CAFs control cancer–stroma interactions through integrin receptor signaling. Here, we isolated CAFs from patients with non‐small‐cell lung cancer (NSCLC) and examined their gene expression profiles. We identified collagen type XI α1 (COL11A1), integrin α11 (ITGA11), and the ITGA11 major ligand collagen type I α1 (COL1A1) among the 390 genes that were significantly enriched in NSCLC‐associated CAFs. Increased ITGA11 expression in cancer stroma was correlated with a poor clinical outcome in patients with NSCLC. Increased expression of fibronectin and collagen type I induced ITGA11 expression in CAFs. The cellular migration of CAFs toward collagen type I and fibronectin was promoted via ERK1/2 signaling, independently of the fibronectin receptor integrin α5β1. Additionally, ERK1/2 signaling induced ITGA11 and COL11A1 expression in cancer stroma. We, therefore, propose that targeting ITGA11 and COL11A1 expressing CAFs to block cancer–stroma interactions may serve as a novel, promising anti‐tumor strategy.
Cancer‐associated fibroblasts (CAFs) regulate cancer progression through the modulation of extracellular matrix (ECM) and cancer cell adhesion. While undergoing a series of phenotypic changes, CAFs control cancer–stroma interactions through integrin receptor signaling. Here, we isolated CAFs from patients with non‐small‐cell lung cancer (NSCLC) and examined their gene expression profiles. We identified collagen type XI α1 (COL11A1), integrin α11 (ITGA11), and the ITGA11 major ligand collagen type I α1 (COL1A1) among the 390 genes that were significantly enriched in NSCLC‐associated CAFs. Increased ITGA11 expression in cancer stroma was correlated with a poor clinical outcome in patients with NSCLC. Increased expression of fibronectin and collagen type I induced ITGA11 expression in CAFs. The cellular migration of CAFs toward collagen type I and fibronectin was promoted via ERK1/2 signaling, independently of the fibronectin receptor integrin α5β1. Additionally, ERK1/2 signaling induced ITGA11 and COL11A1 expression in cancer stroma. We, therefore, propose that targeting ITGA11 and COL11A1 expressing CAFs to block cancer–stroma interactions may serve as a novel, promising anti‐tumor strategy.