ArticleJournal of experimental & clinical cancer research : CR2019
Overexpressed ITGA2 promotes malignant tumor aggression by up-regulating PD-L1 expression through the activation of the STAT3 signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses.PloS one · 2023Pooled it
- CCT2 Promotes Immune Escape in Colorectal Cancer by Regulating the JAK1-STAT3-PD-L1 Axis.Journal of gastroenterology and hepatology · 2026Article
- F7 Drives Gastric Cancer Metastasis Through Anoikis Resistance and Tumor Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- The CD49b (ITGA2) collagen receptor excludes CD8iScience · 2026Article
- Proteomic profiling identifies an oncogene ITGA2 and its downstream targets in gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Computational design and molecular characterization of a multi-epitope peptide vaccine targeting pancreatic cancer.Journal, genetic engineering & biotechnology · 2026Article
- ITGA8 suppresses proliferation and metastasis of lung adenocarcinoma through the inhibition of glycolysis.Scientific reports · 2026Article
- Signatures of Pancreatic Ductal Adenocarcinoma Uncovered by Integrative Multi-Omics Analysis.Cancers · 2026Article
- Article
- Membrane and soluble VTCN1 (B7H4) converge on Src signaling to mediate gemcitabine resistance in intrahepatic cholangiocarcinoma.Theranostics · 2026Article
- Age-stratified analysis of therapeutic, immune, and glycosylation gene expression in colorectal cancer using machine learning.Scientific reports · 2025Article
- Identification of ITGA2 as a methylation-regulated oncogene through a CeRNA network in papillary thyroid carcinoma.Discover oncology · 2025Article
- The Aptamer bi-(AID-1-T) Synergizes with Radiation to Inhibit Proliferation of Human Glioma Cells.Pharmaceutics · 2025Article
- The integrin α2-osteoclast axis: a key driver of bone destruction and therapeutic target in osteosarcoma.Journal of translational medicine · 2025Article
- Tumor treating fields alter local coagulation dynamics in glioblastoma patients.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- ACT001 Inhibits Tumor Progression and Modulates Immune Responses in Non-Small Cell Lung Cancer.Journal of clinical laboratory analysis · 2025Article
- ITGA2 Mediates the Resistance of Hepatocellular Carcinoma to Lenvatinib by Activating the AKT/FOXO3A Signaling Pathway.Cancers · 2025Article
- A novel 5-differentially expressed gene (DEG) signature predicting the prognosis in patients with metastatic liver malignancies and the prognostic and therapeutic potential of SPP1.International journal of clinical oncology · 2025Article
- ID3 enhances PD-L1 expression by restructuring MYC to promote colorectal cancer immune evasion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent studies have reported that Integrin alpha 2 (ITGA2) plays an essential role in tumor cell proliferation, invasion, metastasis, and angiogenesis. An abnormally expressed ITGA2 correlates with unfavorable prognoses in multiple types of cancer. However, the specific mechanism of how ITGA2 contributes to tumorigenesis remains unclear.
methodsThe GEPIA web tool was used to find the clinical relevance of ITGA2 in cancer, and this significance was verified using Western blotting analysis of paired patient tissues and immunohistochemistry of the pancreatic cancer tissue. Functional assays, such as the MTS assay, colony formation assay, and transwell assay, were used to determine the biological role of ITGA2 in human cancer. The relationship between ITGA2 and programmed death-ligand 1 (PD-L1) was examined using Western blot analysis, RT-qPCR assay, and immunohistochemistry. The protein-protein interaction between ITGA2 and STAT3 was detected via co-immunoprecipitation.
resultsOur study showed that ITGA2 was markedly overexpressed in several malignant tumor cells and clinical tissues. Blocking ITGA2 inhibited the proliferation and invasion ability of cancer cells significantly, whereas overexpressed ITGA2 increased the degree of those processes considerably. Additionally, the RNA-seq assay indicated that ITGA2 transcriptionally regulated the expression of PD-L1 in pancreatic cancer. We also demonstrated that ITGA2 interacted with STAT3 and up-regulated the phosphorylation of STAT3; this interaction might involve the mechanism of ITGA2 inducing PD-L1 expression in cancer cells. Our results suggest that ITGA2 plays a critical role in cancer cell progression and the regulation of PD-L1 by activating the STAT3 pathway.
conclusionsWe identified a novel mechanism by which ITGA2 plays a critical role in modulating cancer immune response by transcriptionally increasing the expression of PD-L1 in cancer cells. Thus, targeting ITGA2 is an effective method to enhance the efficacy of checkpoint immunotherapy against cancer.
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