ArticleThe Journal of clinical investigation2013
β4 Integrin signaling induces expansion of prostate tumor progenitors.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 86 citations in OpenAlex.
- Review
- Integrin α6 Targeted Tumor Theranostics.Phenomics (Cham, Switzerland) · 2025Review
- Integrin signaling in tumor biology: mechanisms of intercellular crosstalk and emerging targeted therapies.PeerJ · 2025Review
- The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024Review
- Role of adhesion molecules in cancer and targeted therapy.Science China. Life sciences · 2024Review
- ITGB4 upregulation is associated with progression of lower grade glioma.Scientific reports · 2024Article
- Integrins in cancer stem cells.Frontiers in cell and developmental biology · 2024Review
- Article
- Non B Cell-Derived Immunoglobulins in Lung Epithelial Cells and Lung Cancer.Advances in experimental medicine and biology · 2024Review
- The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery.Biomedicines · 2023Review
- Induction of promyelocytic leukemia zinc finger protein by miR-200c-3p restores sensitivity to anti-androgen therapy in androgen-refractory prostate cancer and inhibits the cancer progression via down-regulation of integrin α3β4.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Identification of a Favorable Prognostic Subgroup in Oral Squamous Cell Carcinoma: Characterization of ITGB4/PD-L1Biomolecules · 2023Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.BMC cancer · 2023Article
- TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway.Gut and liver · 2023Article
- Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo.Journal of hematology & oncology · 2023Article
- Transcriptomic and functional analysis of ANGPTL4 overexpression in pancreatic cancer nominates targets that reverse chemoresistance.Research square · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Targeting c-Met in the treatment of urologic neoplasms: Current status and challenges.Frontiers in oncology · 2023Review
- Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis.Life (Basel, Switzerland) · 2022Article
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The contextual signals that regulate the expansion of prostate tumor progenitor cells are poorly defined. We found that a significant fraction of advanced human prostate cancers and castration-resistant metastases express high levels of the β4 integrin, which binds to laminin-5. Targeted deletion of the signaling domain of β4 inhibited prostate tumor growth and progression in response to loss of p53 and Rb function in a mouse model of prostate cancer (PB-TAg mice). Additionally, it suppressed Pten loss-driven prostate tumorigenesis in tissue recombination experiments. We traced this defect back to an inability of signaling-defective β4 to sustain self-renewal of putative cancer stem cells in vitro and proliferation of transit-amplifying cells in vivo. Mechanistic studies indicated that mutant β4 fails to promote transactivation of ErbB2 and c-Met in prostate tumor progenitor cells and human cancer cell lines. Pharmacological inhibition of ErbB2 and c-Met reduced the ability of prostate tumor progenitor cells to undergo self-renewal in vitro. Finally, we found that β4 is often coexpressed with c-Met and ErbB2 in human prostate cancers and that combined pharmacological inhibition of these receptor tyrosine kinases exerts antitumor activity in a mouse xenograft model. These findings indicate that the β4 integrin promotes prostate tumorigenesis by amplifying ErbB2 and c-Met signaling in tumor progenitor cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.