Anoikis in phenotypic reprogramming of the prostate tumor microenvironment
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Updated: Aug 1, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Prerna R Nepali1, Natasha Kyprianou1,2,3
1Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Abstract:
Prostate cancer is one of the most common malignancies in males wherein 1 in 8 men are diagnosed with this disease in their lifetime. The urgency to find novel therapeutic interventions is associated with high treatment resistance and mortality rates associated with castration-resistant prostate cancer. Anoikis is an apoptotic phenomenon for normal epithelial or endothelial cells that have lost their attachment to the extracellular matrix (ECM). Tumor cells that lose their connection to the ECM can die via apoptosis or survive via anoikis resistance and thus escaping to distant organs for metastatic progression. This review discusses the recent advances made in our understanding of the signaling effectors of anoikis in prostate cancer and the approaches to translate these mechanistic insights into therapeutic benefits for reducing lethal disease outcomes (by overcoming anoikis resistance). The prostate tumor microenvironment is a highly dynamic landscape wherein the balance between androgen signaling, cell lineage changes, epithelial-mesenchymal transition (EMT), extracellular matrix interactions, actin cytoskeleton remodeling as well as metabolic changes, confer anoikis resistance and metastatic spread. Thus, these mechanisms also offer unique molecular treatment signatures, exploitation of which can prime prostate tumors to anoikis induction with a high translational significance.
Insights
Prostate cancer cells can survive detachment from the extracellular matrix (ECM) through anoikis resistance, promoting metastasis. Targeting these resistance mechanisms offers new therapeutic strategies for lethal prostate cancer.
Area of Science:
- Oncology
- Cell Biology
- Cancer Metastasis
Background:
- Prostate cancer is a prevalent malignancy with significant mortality, particularly castration-resistant forms.
- Anoikis, a form of apoptosis, normally eliminates detached epithelial cells; however, cancer cells can develop resistance.
- Anoikis resistance is a critical factor in prostate cancer progression and metastasis.
Purpose of the Study:
- To review recent advances in understanding anoikis signaling in prostate cancer.
- To explore therapeutic strategies targeting anoikis resistance for improved outcomes.
- To highlight the role of the tumor microenvironment in anoikis resistance and metastasis.
Main Methods:
- Literature review of signaling pathways involved in anoikis.
- Analysis of the prostate tumor microenvironment's contribution to anoikis resistance.
- Discussion of potential therapeutic targets and translational approaches.
Main Results:
- Anoikis resistance in prostate cancer is linked to complex interactions within the tumor microenvironment.
- Key factors include androgen signaling, epithelial-mesenchymal transition (EMT), ECM interactions, and metabolic changes.
- These mechanisms provide potential molecular signatures for targeted therapies.
Conclusions:
- Understanding anoikis signaling is crucial for developing novel prostate cancer treatments.
- Targeting anoikis resistance mechanisms can overcome treatment resistance and reduce lethal disease.
- Exploiting these pathways offers significant translational potential for clinical application.
