Connexins, important players in the dissemination of prostate cancer cells

Biochim Biophys Acta Biomembr. 2018 Jan;1860(1):202-215. doi: 10.1016/j.bbamem.2017.06.020. Epub 2017 Jul 8.

Abstract

Over the past 50years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoural profile for most of invasion and dissemination steps to secondary sites. We report here the current knowledge on the function of Cxs during PCa cells migration, cytoskeletal dynamics, proteinases activities and the cross talk with the surrounding stromal cells in the microenvironment of the tumour and the bones. In addition, we discuss the role of Cxs in the bone tropism even if the prostate model is rarely used to study the complete sequence of cancer dissemination compared to breast cancer or melanoma. Even if not yet fully understood, these recent findings on Cxs provide new insights into their molecular mechanisms associated with progression and bone targeted behaviour of PCa. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.

Keywords: Bone metastasis; Connexin43; GJIC; Invasion; Migration; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Connexin 43* / genetics
  • Connexin 43* / metabolism
  • Gap Junctions* / genetics
  • Gap Junctions* / metabolism
  • Gap Junctions* / pathology
  • Humans
  • Male
  • Neoplasm Metastasis
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Tumor Microenvironment*

Substances

  • Connexin 43
  • Neoplasm Proteins