ArticleBosnian journal of basic medical sciences2020
Integrin beta 4 (ITGB4) and its tyrosine-1510 phosphorylation promote pancreatic tumorigenesis and regulate the MEK1-ERK1/2 signaling pathway.
Article in Bosnian journal of basic medical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 36 citations in OpenAlex.
- Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas.Journal of biochemistry · 2026Article
- ITGB4 up-regulated by STAT3 reduces the sensitivity of bladder cancer to cisplatin by suppressing p53.British journal of cancer · 2026Article
- A pyroptosis-related molecular signature stratifies prognosis and highlights GSDMB-mediated malignancy in intrahepatic cholangiocarcinoma.Biology direct · 2026Article
- Exploring the interactions of integrins and CEACAM6 (Review).Experimental and therapeutic medicine · 2025Review
- Deciphering pre-existing and induced 3D genome architecture changes involved in constricted melanoma migration.iScience · 2025Article
- ITGB4 Serves as an Identification and Prognosis Marker Associated with Immune Infiltration in Small Cell Lung Carcinoma.Molecular biotechnology · 2024Article
- IDH1-mutant metabolite D-2-hydroxyglutarate inhibits proliferation and sensitizes glioma to temozolomide via down-regulating ITGB4/PI3K/AKT.Cell death discovery · 2024Article
- Preclinical efficacy of CBR-5884 against epithelial ovarian cancer cells by targeting the serine synthesis pathway.Discover oncology · 2024Article
- Identification of ITGB4 as a novel tumor promoting gene in lung adenocarcinoma (LUAD).Oncology reports · 2024Article
- ITGB4 upregulation is associated with progression of lower grade glioma.Scientific reports · 2024Article
- The mechanism of ITGB4 in tumor migration and invasion.Frontiers in oncology · 2024Review
- Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.Frontiers in cellular and infection microbiology · 2024Article
- Do extracellular vesicles have specific target cells?; Extracellular vesicle mediated embryo maternal communication.Frontiers in molecular biosciences · 2024Article
- Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.BMC cancer · 2023Article
- SPTBN2 regulates endometroid ovarian cancer cell proliferation, invasion and migration via ITGB4‑mediated focal adhesion and ECM receptor signalling pathway.Experimental and therapeutic medicine · 2023Article
- PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis.Cancers · 2023Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.Research square · 2023Article
- Integrin alpha 6 is upregulated and drives hepatocellular carcinoma progression through integrin α6β4 complex.International journal of cancer · 2022Article
- Integrin Beta 4E Promotes Endothelial Phenotypic Changes and Attenuates Lung Endothelial Cell Inflammatory Responses.Frontiers in physiology · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer is the fourth leading cause of cancer death, with a 5-year survival rate of only 1-4%. Integrin-mediated cell adhesion is critical for the initiation, progression, and metastasis of cancer. In this study we investigated the role of integrin b4 (ITGB4) and its phosphorylation at tyrosine Y1510 (p-ITGB4-Y1510) in the tumorigenesis of pancreatic cancer. We analyzed the expression of ITGB4 and p-ITGB4-Y1510 in pancreatic cancer tissue and cell lines using immunohistochemistry, Western blot, or semi-quantitative reverse transcription PCR. ITGB4 and p-ITGB4-Y1510 were highly expressed in pancreatic cancer (n = 176) compared with normal pancreatic tissue (n = 171). High p-ITGB4-Y1510 expression correlated with local invasion and distant metastasis of pancreatic cancer, and high ITGB4 was significantly associated with poor survival of patients. Inhibition of ITGB4 by siRNA significantly reduced migration and invasion of PC-1.0 and AsPC-1 cells. Overexpression of the mutant ITGB4-Y1510A (a mutation of tyrosine to alanine at 1510 position) in PC-1.0 and AsPC-1 cells not only blocked the ITGB4 phosphorylation at Y1510 but also suppressed the expression of ITGB4 (p < 0.05 vs. wild-type ITGB4). The transfection of PC-1.0 and AsPC-1 cells with ITGB4-Y1510A significantly decreased the level of p-mitogen-activated protein kinase kinase (MEK)1 (T292) and p-extracellular signal-regulated kinase (ERK)1/2 but did not affect the level of p-MEK1 (T386) and p-MEK2 (T394). Overall, our study showed that ITGB4 and its phosphorylated form promote cell migration and invasion in pancreatic cancer and that p-ITGB4-Y1510 regulates the downstream MEK1-ERK1/2 signaling cascades. Targeting ITGB4 or its phosphorylation at Y1510 may be a novel therapeutic option for pancreatic cancer.
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