Integrin-α5 expression and its role in non-small cell lung cancer progression

  • Cancer Sci. 2025 Feb;116(2):406-419. doi: 10.1111/cas.16416.
Mirei Ka  1 ,  Yoko Matsumoto  2 ,  Takahiro Ando  2 ,  Munetoshi Hinata  3 ,  Qian Xi  1 ,  Yuriko Sugiura  2 ,  Takahiro Iida  4 ,  Natsuki Nakagawa  2 ,  Masakatsu Tokunaga  2 ,  Kousuke Watanabe  5 ,  Masanori Kawakami  2 ,  Tetsuo Ushiku  3 ,  Masaaki Sato  4 ,  Katsutoshi Oda  1 ,  Hidenori Kage  2
Affiliations
  • 1. Division of Integrative Genomics, The University of Tokyo, Tokyo, Japan.
  • 2. Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan.
  • 3. Department of Pathology, The University of Tokyo, Tokyo, Japan.
  • 4. Department of Thoracic Surgery, The University of Tokyo, Tokyo, Japan.
  • 5. Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
PMID: 39581761 DOI: 10.1111/cas.16416
Abstract

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.

Keywords
adhesion; integrin alpha‐5; migration; non‐small cell lung cancer; postoperative recurrence.
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