Ka Mirei, Matsumoto Yoko, Ando Takahiro, Hinata Munetoshi, Xi Qian, Sugiura Yuriko, Iida Takahiro, Nakagawa Natsuki, Tokunaga Masakatsu, Watanabe Kousuke, Kawakami Masanori, Ushiku Tetsuo, Sato Masaaki, Oda Katsutoshi, Kage Hidenori
Division of Integrative Genomics, The University of Tokyo, Tokyo, Japan.
Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan.
Cancer Sci. 2025 Feb;116(2):406-419. doi: 10.1111/cas.16416. Epub 2024 Nov 24.
Integrins are transmembrane receptors that facilitate cell adhesion to the extracellular matrix and neighboring cells. Aberrant expression of integrins has been associated with tumor progression and metastasis in various cancer types. Integrin alpha-5 (ITGA5) is an integrin subtype that serves as a receptor for fibronectin, fibrinogen, and fibrillin-1. The purpose of this study was to elucidate how ITGA5 expression plays a role in human non-small cell lung cancer (NSCLC). Our clinical data, along with data retrieved from The Cancer Genome Database (TCGA), revealed that high ITGA5 expression in NSCLC patients was associated with a lower recurrence-free survival and overall survival. In our in vitro functional assays, ITGA5 overexpression in human NSCLC cell lines resulted in increased cell size, adhesion, and migration properties, while knockdown of ITGA5 restored the phenotypes. Correspondingly, knockdown and inhibition of ITGA5 in endogenously high-expressing NSCLC cell lines resulted in decreased cell size, adhesion, migration, and proliferation. The antiproliferative effect was also confirmed by a reduction in Ki-67 without discernible changes in apoptosis. Collectively, these findings reveal the significant role of ITGA5 in various functional behaviors in NSCLC, providing a potential therapeutic target for NSCLC patients with high ITGA5 expression.
整合素是跨膜受体,可促进细胞与细胞外基质及相邻细胞的黏附。整合素的异常表达与多种癌症类型的肿瘤进展和转移相关。整合素α-5(ITGA5)是一种整合素亚型,可作为纤连蛋白、纤维蛋白原和原纤蛋白-1的受体。本研究的目的是阐明ITGA5表达如何在人类非小细胞肺癌(NSCLC)中发挥作用。我们的临床数据以及从癌症基因组数据库(TCGA)检索到的数据显示,NSCLC患者中ITGA5的高表达与较低的无复发生存率和总生存率相关。在我们的体外功能试验中,人类NSCLC细胞系中ITGA5的过表达导致细胞大小、黏附及迁移特性增加,而ITGA5的敲低则恢复了这些表型。相应地,在内源性高表达的NSCLC细胞系中敲低和抑制ITGA5导致细胞大小、黏附、迁移和增殖减少。Ki-67的减少证实了抗增殖作用,而凋亡无明显变化。总体而言,这些发现揭示了ITGA5在NSCLC各种功能行为中的重要作用,为ITGA5高表达的NSCLC患者提供了潜在的治疗靶点。