Untitled

Abstract

Gap junctional intercellular communication (GJIC) is a form of cell-cell communication mediating the exchange of small molecules between neighboring cells. Gap junctions (GJs) are formed by connexins (Cxs), and are subject to tight and dynamic regulation. They are involved in the cell cycle, differentiation, and cell signaling. The loss of Cxs and GJs is a hallmark of carcinogenesis, while their induction in cancer cells leads to a reversal of the cancer phenotype, induction of differentiation, and regulation of cell growth. On the basis of the observations about Cx loss in breast cancer, this review examines Cxs' involvement in breast cancer metastasis. Previous work indicates that Cx expression is inversely correlated to metastatic potential. This is probably because of the loss of cooperation between neighboring cells, leading to cell heterogeneity and cell dissociation in the tumor. The possible involvement of Cx activity during metastasis will be discussed.

Connexin 43 in the development and progression of breast cancer: What's the connection? (Review)

“…However, evidence supports both pro- and anti-metastatic roles for Cx43 and many reports indicate that levels of Cx43 are both elevated and reduced in breast cancer (7,9,11–24). Consequently, there has been prominent debate in breast cancer regarding whether Cx43 promotes or inhibits breast cancer progression and metastasis because experimental findings have been somewhat contradictory (11–21). …”

“…Studies that examine human breast cancer tissue suggest that levels of Cx43 either increase or decrease with cancer stage (7–10). Studies also suggest that Cx43 localization to gap junctions could play a part in determining disease severity, suggesting that preserving Cx43 gap junctions could be an important distinction between normal and malignant breast epithelial cells (7,10,11,23,25–28). However, evidence supports both pro- and anti-metastatic roles for Cx43 and many reports indicate that levels of Cx43 are both elevated and reduced in breast cancer (7,9,11–24).…”

“…Studies also suggest that Cx43 localization to gap junctions could play a part in determining disease severity, suggesting that preserving Cx43 gap junctions could be an important distinction between normal and malignant breast epithelial cells (7,10,11,23,25–28). However, evidence supports both pro- and anti-metastatic roles for Cx43 and many reports indicate that levels of Cx43 are both elevated and reduced in breast cancer (7,9,11–24). Consequently, there has been prominent debate in breast cancer regarding whether Cx43 promotes or inhibits breast cancer progression and metastasis because experimental findings have been somewhat contradictory (11–21).…”

Connexin43 pseudogene is expressed in tumor cells and inhibits growth

“…Also, it is increasingly evident that connexins are involved in cancer (Vine and Bertram, 2002). In particular, connexins' role in breast cancer is under scrutiny (Carystinos et al, 2001).…”

Physiological and pathological implications of retinoid action in the endometrium

“…Endometrial CX43 may be regulated by hormonal changes, and the progesterone and estrogen levels in serum are reported to determine the expression levels of CX43 in the endometrium (Yu et al 2014b, Winterhager & Kidder 2015. RA and other retinoids enhance GJIC and CX43 expression levels in numerous cell types, certain human cancer cell types, mouse fibroblasts and rat liver cells, through transcriptional and translational mechanisms (Stahl & Sies 1998, Carystinos et al 2001. When treated with RA, CX43 expression in human endometrial stromal cells shows a dose-dependent increase at the mRNA and protein levels (Tanmahasamut & Sidell 2005) (Table 2).…”