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The role of connexins in prostate cancer promotion and progression

Nature Reviews Urology volume 9, pages 274–282 (2012)Cite this article

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Abstract

Prostate cancer is a prevalent disease that is characterized by a presumably long latency period and a moderate propensity to metastasize. Although a range of mechanisms have been implicated in prostate carcinogenesis, the factors determining the initiation of metastasis remain obscure. The synchronized function of prostate cells depends on their metabolic and electrical coupling; disturbance of these functions has long been suggested to be integral to prostate carcinogenesis. However, although connexins form intercellular channels involved in gap-junction-mediated intercellular coupling (GJIC), whether these proteins also have GJIC-independent roles in cancer progression and metastasis remains a matter of debate. Some data indicate a correlation between connexin expression and the invasive potential of prostate cancer cells, which points to stage-specific functions of connexins during prostate cancer development. For example, restoration of connexin expression seems to be crucial for the formation of invasive cell subsets within heterogeneous prostate cancer cell populations that have undergone aberrant differentiation. Consequently, the clinical application of therapeutic and prophylactic approaches focused on the modulation of connexin expression in prostate cancer cells should be reconsidered.

Key Points

  • Connexins are integral membrane proteins that form gap junctions, which are clusters of aqueous channels that directly link cytoplasmic compartments of neighboring cells and enable intercellular communication

  • Connexins can also modulate cellular traits crucial for cancer development, such as proliferation and migration, in a manner independent of gap junctions

  • The differential expression and functional incompatibility of connexons composed of connexin 32 and connexin 43 establish functional compartments within the prostate epithelium that determine its synchronized action

  • Inhibition of connexin expression promotes prostate carcinogenesis, whereas restoration of connexin function in subpopulations of prostate cancer cells seems to drive prostate cancer progression and metastasis

  • Treatment regimens that target connexin expression and function in prostate cancer cells should take into account the stage-specific roles of connexins and gap junctions in prostate cancer development

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Figure 1: Model of the maintenance of prostate epithelial parenchyma.
Figure 2: Gap-junction-dependent and gap-junction-independent functions of connexins.
Figure 3: Hypothetical mechanism of the stage-dependent involvement of connexins in prostate cancer progression.

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Acknowledgements

The current authors' research on the topics discussed in this review is supported by the Polish National Science Centre (grant 2011/01/B/NZ3/00004). The authors' research is also financed by Polish Ministry of Scientific Research and Higher Education, (N N302 061936 and N N301 050236) and the European Regional Development Fund within the Operational Programme Innovative Economy (grant UDA-POIG.01.03.01-14-036/09-00). The Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University is a beneficiary of structural funds from the European Union (grant POIG.02.01.00-12-064/08 and POIG 01.02-00-109/99).

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  1. Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387, Kraków, Poland

    Jarosław Czyż, Katarzyna Szpak & Zbigniew Madeja

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  1. Jarosław Czyż
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J. Czyż, K. Szpak and Z. Madeja researched data for this article. J. Czyż wrote the manuscript, K. Szpak designed the figures and all authors reviewed and edited the article before submission.

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Correspondence to Jarosław Czyż.

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Czyż, J., Szpak, K. & Madeja, Z. The role of connexins in prostate cancer promotion and progression. Nat Rev Urol 9, 274–282 (2012). https://doi.org/10.1038/nrurol.2012.14

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