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Review
. 2020 Dec 23:10:599383.
doi: 10.3389/fonc.2020.599383. eCollection 2020.

Connexins in Lung Cancer and Brain Metastasis

Kai-Jun Luo  1   2 , Chang-Xu Chen  1   2 , Jia-Peng Yang  3   4 , Yun-Chao Huang  3   4 , Eduardo R Cardenas  5 , Jean X Jiang  5
Affiliations
Review

Connexins in Lung Cancer and Brain Metastasis

Kai-Jun Luo et al. Front Oncol. .

Abstract

Connexins (Cxs) are involved in the brain metastasis of lung cancer cells. Thus, it is necessary to determine whether gap junction-forming Cxs are involved in the communication between lung cancer cells and the host cells, such as endothelial cells, forming the brain-blood-barrier, and cells in the central nervous system. Data from multiple studies support that Cxs function as tumor suppressors during lung cancer occurrence. However, recent evidence suggests that during metastasis to the brain, cancer cells establish communication with the host. This review discusses junctional or non-junctional hemichannel studies in lung cancer development and brain metastasis, highlighting important unanswered questions and controversies.

Keywords: astrocytes; connexin; endothelial cells; gap junction; hemichannel; lung cancer brain metastasis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Connexins (Cxs) in human lung cancer tissue and its Cx-channels. In normal lung tissues, 21 connexin genes, mRNA, and protein have been detected in the human genome, junctional hemichannel, and hemichannels (1, 2).
Figure 2
Figure 2
Endothelial Connexins (Cxs) allow lung cancer diapedesis. In blood vessels, endothelial Cx37, Cx40, and Cx43 contribute to the of lung tumor cells (40, 45, 46).
Figure 3
Figure 3
Astrocyte Cx43 interaction with brain metastases lung tumor. (A) At the occurrence of lung cancer brain metastasis, astrocytes kill most lung cancer cells that cross the blood–brain-barrier; few lung cancer cells survive form Cx43 gap junctions with astrocytes. (B) In the late stage of brain metastasis, Cx43 gap junctions between astrocytes and surviving lung cancer cells confer resistance against chemotherapy (53, 58).
See this image and copyright information in PMC

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