ArticleMolecular cancer research : MCR2013
Targeting constitutively activated β1 integrins inhibits prostate cancer metastasis.
Article in Molecular cancer research : MCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 91 citations in OpenAlex.
- Integrative Proteomic Analysis Implicates Inhibition of Intracellular Protein Trafficking in Therapy-Induced Migrastasis in Prostate Cancer.Proteomes · 2026Article
- Canonical Wnt signaling in the regulation of prostate cancer stem cells: a key driver of castration-resistant prostate cancer and a therapeutic opportunity.Journal of translational medicine · 2026Review
- Extracellular Domain Shedding of TROP2 Activates EGFR Signaling to Drive Prostate Cancer Metastasis.Cancer research · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Irradiation of prostate cancer alters circulating small extracellular vesicle functions.Scientific reports · 2025Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer.Antibodies (Basel, Switzerland) · 2025Article
- Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.Cancers · 2024Review
- The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment.Cell biochemistry and biophysics · 2023Review
- PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.Molecular oncology · 2023Article
- The role of integrin family in bone metabolism and tumor bone metastasis.Cell death discovery · 2023Review
- The Emerging Role of Cell Adhesion Molecules on Benign Prostatic Hyperplasia.International journal of molecular sciences · 2023Review
- In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models.Biomolecules · 2023Review
- Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types - A one research lab re-evaluation.Computational and structural biotechnology journal · 2023Article
- Anoikis in phenotypic reprogramming of the prostate tumor microenvironment.Frontiers in endocrinology · 2023Review
- EnhancingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP/TAZ inhibition.Oncogene · 2022Article
- The Solute Carrier MFSD1 Decreases the Activation Status of β1 Integrin and Thus Tumor Metastasis.Frontiers in oncology · 2022Article
- Statins reduce castration-induced bone marrow adiposity and prostate cancer progression in bone.Oncogene · 2021Article
- Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance.International journal of molecular sciences · 2021Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Disseminated prostate cancer cells must survive in circulation for metastasis to occur. Mechanisms by which these cells survive are not well understood. By immunohistochemistry of human tissues, we found that levels of β1 integrins and integrin-induced autophosphorylation of FAK (pFAK-Y397) are increased in prostate cancer cells in primary prostate cancer and lymph node metastases, suggesting that β1 integrin activation occurs in metastatic progression of prostate cancer. A conformation-sensitive antibody, 9EG7, was used to examine β1 integrin activation. We found that β1 integrins are constitutively activated in highly metastatic PC3 and PC3-mm2 cells, with less activation in low metastatic LNCaP and C4-2B4 cells. Increased β1 integrin activation as well as the anoikis resistance in prostate cancer cells correlated with metastatic potential in vivo. Knockdown of β1 integrin abrogated anoikis resistance in PC3-mm2 cells. In agreement with β1 integrin activation, PC3-mm2 cells strongly adhered to type I collagen and fibronectin, a process inhibited by the β1 integrin-neutralizing antibody mAb 33B6. mAb 33B6 also inhibited the phosphorylation of β1 integrin downstream effectors, focal adhesion kinase (FAK) and AKT, leading to a 3-fold increase in PC3-mm2 apoptosis. Systemic delivery of mAb 33B6 suppressed spontaneous metastasis of PC3-mm2 from the prostate to distant lymph nodes following intraprostatic injection and suppressed metastasis of PC3-mm2 to multiple organs following intracardiac injection. Thus, constitutively activated β1 integrins play a role in survival of PC3-mm2 cells in circulation and represent a potential target for metastasis prevention.
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