ArticleMolecular oncology2019
Integrin α5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.
Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- DTX1 Regulates Aortic Dissection Progression by Modulating Vascular Smooth Muscle Cell Phenotypic Switching via Ubiquitination of ITGA5.Cardiovascular drugs and therapy · 2026Article
- Alpha 5 integrin as a prognostic biomarker for survival in carcinomas: a systematic review.Discover oncology · 2025Review
- Article
- Identification and Experimental Validation of Oxidative Stress-Related Biomarkers in Ulcerative Colitis Using Machine Learning.Journal of inflammation research · 2025Article
- Identifying Spatial Co-occurrence in Healthy and InflAmed tissues (ISCHIA).Molecular systems biology · 2024Article
- Based on Weighted Gene Co-Expression Network Analysis Reveals the Hub Immune Infiltration-Related Genes Associated with Ulcerative Colitis.Journal of inflammation research · 2024Article
- Targeting integrin α5 in fibroblasts potentiates colorectal cancer response to PD-L1 blockade by affecting extracellular-matrix deposition.Journal for immunotherapy of cancer · 2023Article
- Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma.Protoplasma · 2023Article
- Cancer immune exclusion: breaking the barricade for a successful immunotherapy.Frontiers in oncology · 2023Review
- Article
- Nitric-Oxide Synthase trafficking inducer (NOSTRIN) is an emerging negative regulator of colon cancer progression.BMC cancer · 2022Article
- Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer.Frontiers in genetics · 2022Article
- Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression.World journal of gastrointestinal oncology · 2021Review
- Article
- ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors.BMC cancer · 2021Article
- A Prognostic Model Based on Nine DNA Methylation-Driven Genes Predicts Overall Survival for Colorectal Cancer.Frontiers in genetics · 2021Article
- An Inflammatory Response-Related Gene Signature Can Impact the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Evolution of Mutational Landscape and Tumor Immune-Microenvironment in Liver Oligo-Metastatic Colorectal Cancer.Cancers · 2020Article
- [Integrin α5 silencing inhibits proliferation, invasion and metastasis of human liver cancer Bel-7404 cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- miR-27b Suppresses Tongue Squamous Cell Carcinoma Epithelial-Mesenchymal Transition by Targeting ITGA5.OncoTargets and therapy · 2020Article
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumorigenesis of colorectal cancer (CRC) is a complicated process, involving interactions between cancer cells and the microenvironment. The role of α5 integrin subunit in CRC remains controversial, and previous studies mainly focused on cancer cells. Herein, we report an important role of α5 in stroma fibroblasts in the tumorigenesis of CRC. The expression of α5 was found to be located in colorectal tumor stroma rather than in epithelia cancer cells. Immunofluorescence colocalization and gene correlation analysis confirmed that α5 was mainly expressed in cancer-associated fibroblasts (CAFs). Moreover, experimental evidence showed that α5 expression was required for the tumor-promoting effect of fibroblast cells. In an in vivo xenograft nude mice model, α5 depletion in fibroblasts dramatically suppressed fibroblast-induced tumor growth. In an in vitro cell coculture assay, α5 depletion or knockdown reduced the ability of fibroblasts to promote cancer cell migration and invasion compared with wild-type fibroblasts; moreover, we observed that the expression and assembly of fibronectin were downregulated after α5 depletion or knockdown in fibroblasts. Analysis of the RNA-Seq data of the Cancer Genome Atlas cohort revealed that high expression of ITGA5 (α5 integrin subunit) was correlated with poor overall survival in colorectal adenocarcinoma, which was further confirmed by immunohistochemistry in an independent cohort of 355 patients. Thus, our study identifies α5 integrin subunit as a novel stroma molecular marker for colorectal adenocarcinoma, offers a fresh insight into colorectal adenocarcinoma progression, and shows that α5 expression in stroma fibroblasts underlies its ability to promote the tumorigenesis of colorectal adenocarcinoma.
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