ArticleCancer research2016
αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Beyond DNA damage: 3D tumor models and the integrin mechanobiology of radioresistance.Journal of experimental & clinical cancer research : CR · 2026Review
- An orally bioavailable pan-αv/α5β1 integrin antagonist prevents aggressive prostate cancer progression via suppressing both oncogenic signals and CD47-mediated immune escape.Molecular cancer · 2026Article
- Review
- Expression of the αVβ3 integrin affects prostate cancer sEV cargo and density and promotes sEV pro-tumorigenic activity in vivo through a GPI-anchored receptor, NgR2.Journal of extracellular vesicles · 2024Article
- Review
- RNA N6-methyladenosine modification in regulating cancer stem cells and tumor immune microenvironment and its implication for cancer therapy.Journal of cancer research and clinical oncology · 2023Review
- The Emerging Role of Cell Adhesion Molecules on Benign Prostatic Hyperplasia.International journal of molecular sciences · 2023Review
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Small extracellular vesicle-mediatedCancer biology & therapy · 2022Article
- The NOGO receptor NgR2, a novel αVβ3 integrin effector, induces neuroendocrine differentiation in prostate cancer.Scientific reports · 2022Article
- Article
- Prostate Cancer Epigenetic Plasticity and Enhancer Heterogeneity: Molecular Causes, Consequences and Clinical Implications.Advances in experimental medicine and biology · 2022Review
- IFIT3 (interferon induced protein with tetratricopeptide repeats 3) modulates STAT1 expression in small extracellular vesicles.The Biochemical journal · 2021Article
- Integrins regulate stemness in solid tumor: an emerging therapeutic target.Journal of hematology & oncology · 2021Review
- Article
- A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer.Research and reports in urology · 2021Review
- Article
- Small extracellular vesicles modulated by αVβ3 integrin induce neuroendocrine differentiation in recipient cancer cells.Journal of extracellular vesicles · 2020Article
- Clinical Significance of C-X-C Motif Chemokine Receptor 4 and Integrin αvβ6 Expression in Breast Cancer.Journal of breast cancer · 2020Article
- Integrin Alpha V in Urine: A Novel Noninvasive Marker for Prostate Cancer Detection.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
Androgen receptor signaling fuels prostate cancer and is a major therapeutic target. However, mechanisms of resistance to therapeutic androgen ablation are not well understood. Here, using a prostate cancer mouse model, Pten(pc-/-), carrying a prostate epithelial-specific Pten deletion, we show that the αvβ6 integrin is required for tumor growth in vivo of castrated as well as of noncastrated mice. We describe a novel signaling pathway that couples the αvβ6 integrin cell surface receptor to androgen receptor via activation of JNK1 and causes increased nuclear localization and activity of androgen receptor. This downstream kinase activation by αvβ6 is specific for JNK1, with no involvement of p38 or ERK kinase. In addition, differential phosphorylation of Akt is not observed under these conditions, nor is cell morphology affected by αvβ6 expression. This pathway, which is specific for αvβ6, because it is not regulated by a different αv-containing integrin, αvβ3, promotes upregulation of survivin, which in turn supports anchorage-independent growth of αvβ6-expressing cells. Consistently, both αvβ6 and survivin are significantly increased in prostatic adenocarcinoma, but are not detected in normal prostatic epithelium. Neither XIAP nor Bcl-2 is affected by αvβ6 expression. In conclusion, we show that αvβ6 expression is required for prostate cancer progression, including castrate-resistant prostate cancer; mechanistically, by promoting activation of JNK1, the αvβ6 integrin causes androgen receptor-increased activity in the absence of androgen and consequent upregulation of survivin. These preclinical results pave the way for further clinical development of αvβ6 antagonists for prostate cancer therapy. Cancer Res; 76(17); 5163-74. ©2016 AACR.
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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.