ArticleOncogene2020
Androgen receptor-induced integrin α6β1 and Bnip3 promote survival and resistance to PI3K inhibitors in castration-resistant prostate cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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
20 citing papers in PubMed, 27 citations in OpenAlex.
- Molecular diversity of mitochondrial autophagy receptors: context-dependent effects in human health and disease.Cell death discovery · 2026Review
- ODC1 Polyamine Metabolism Drives Prostate Cancer via AKT and Splicing.Journal of cellular and molecular medicine · 2026Article
- The role of laminins in cancer pathobiology: a comprehensive review.Journal of translational medicine · 2025Review
- The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment.Journal of translational medicine · 2024Article
- Microfluidic-based human prostate-cancer-on-chip.Frontiers in bioengineering and biotechnology · 2024Article
- The characteristics and the multiple functions of integrin β1 in human cancers.Journal of translational medicine · 2023Review
- Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer.Aging · 2023Article
- Review
- Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer.Journal of clinical medicine · 2023Article
- The Emerging Role of Cell Adhesion Molecules on Benign Prostatic Hyperplasia.International journal of molecular sciences · 2023Review
- MMP11 and MMP14 contribute to the interaction between castration-resistant prostate cancer and adipocytes.American journal of cancer research · 2023Article
- Establishment of a novel prognostic prediction model through bioinformatics analysis for prostate cancer based on ferroptosis-related genes and its application in immune cell infiltration.Translational andrology and urology · 2022Article
- Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth.Autophagy · 2022Article
- Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.Journal of experimental & clinical cancer research : CR · 2022Review
- Growth, Proliferation and Metastasis of Prostate Cancer Cells Is Blocked by Low-Dose Curcumin in Combination with Light Irradiation.International journal of molecular sciences · 2021Article
- Review
- EBV-LMP1 promotes radioresistance by inducing protective autophagy through BNIP3 in nasopharyngeal carcinoma.Cell death & disease · 2021Article
- Review
- Employing hypoxia characterization to predict tumour immune microenvironment, treatment sensitivity and prognosis in hepatocellular carcinoma.Computational and structural biotechnology journal · 2021Article
- BNIP3 in Lung Cancer: To Kill or Rescue?Cancers · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The androgen receptor (AR) is the major driver of prostate cancer growth and survival. However, almost all patients relapse with castration-resistant disease (CRPC) when treated with anti-androgen therapy. In CRPC, AR is often aberrantly activated independent of androgen. Targeting survival pathways downstream of AR could be a viable strategy to overcome CRPC. Surprisingly, little is known about how AR drives prostate cancer survival. Furthermore, CRPC tumors in which Pten is lost are also resistant to eradication by PI3K inhibitors. We sought to identify the mechanism by which AR drives tumor survival in CRPC to identify ways to overcome resistance to PI3K inhibition. We found that integrins α6β1 and Bnip3 are selectively elevated in CRPC downstream of AR. While integrin α6 promotes survival and is a direct transcriptional target of AR, the ability of AR to induce Bnip3 is dependent on adhesion to laminin and integrin α6β1-dependent nuclear translocation of HIF1α. Integrins α6β1 and Bnip3 were found to promote survival of CRPC cells selectively on laminin through the induction of autophagy and mitophagy. Furthermore, blocking Bnip3 or integrin α6β1 restored sensitivity to PI3K inhibitors in Pten-negative CRPC. We identified an AR driven pathway that cooperates with laminin and hypoxia to drive resistance to PI3K inhibitors. These findings can help explain in part why PI3K inhibitors have failed in clinical trials to overcome AR-dependent CRPC.
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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.