Table 1.

Summary of the role of Cx43 with specific cell combinations in cancer pathology.

Cell Combination	Form of Cx	Transmitter or Partner Molecule	Effect on Malignant Behavior and Mechanisms Suggested to Be Occurred in Cancer Cells	Ref.
Breast cancer–Osteocyte	HCs	ATP	Released ATP from osteocyte inhibits growth, migration and invasion ability of breast cancer cells	[9]
Mesothelioma–Mesothelioma	Cx molecule (C-terminal)	Src, Bax, JNK	Increasing level of Cx43 in malignant mesothelioma cell enhances sensitivity against cisplatin and sunitinib treatment	[11,12,13]
Leukemic cell–BMSCs	GJ	-	GJ between Cx43- overexpressed BMSCs and leukemic cells induced apoptosis in leukemic cells due to caspase 3/7 activation	[14,15]
Glioblastoma–HMEC	GJ	miR-145-5b	miR-145-5b from HMEC is transferred to glioblastoma (U87 cells) which decrease cancer proliferation	[22]
Colon cancer–HMEC	GJ	miR-145-5b	miR-145-5b from HMEC is permitted to be transferred to cancer cells (SW480 cells) and up-regulated Cx43 expression, which inhibits proangiogenic effect of cancer cells	[23]
Glioma–Glioma	GJ, Cx molecule (extracellular loop and/or C-terminal)	miR-5096	GJ between glioma–glioma has anti-invasive effect	[24,25]
Glioblastoma–HMEC	GJ	miR-5096	mir-5096 from glioblastoma is transferred to HMEC increases proangiogenic effect of glioblastoma	[26]
Glioma–Glioma	GJ, Cx molecule (C-terminal)	Bcl-2, Bax	Increasing level of Cx43 in glioma cell enhances resistance against temozolomide treatmentIncreasing level of Cx43 in glioma cell enhances resistance against temozolomide treatment	[27]
Microglia–Astrocyte	GJ, HCs	IL-1β, TNF-α	Intercellular diffusion of glucose in CNS via GJ composed of Cx43 between astrocytes is downregulated by cytokines secreted from HCs of microglia. Oppositely, when glucose uptake in each astrocyte is increased, it switches the cell to be a reactive astrocyte.	[3]
Glioma–Astrocyte, Astrocyte–Astrocyte	GJ, Cx molecule (extracellular loop and/or C-terminal)	miR-5096	Glioma–astrocyte and astrocyte–astrocyte promotes glioma invasion	[25,28]
Glioblastoma–HMEC	GJ	miR-5096	mir-5096 from glioblastoma (U-87 cells) to HMEC increases proangiogenic effect	[26]
Melanoma–Astrocyte	GJ	-	Direct contact with astrocyte up-regulates invasion of cancer cells and drug resistance	[29]
Breast cancer–Astrocyte, Lung cancer–Astrocyte	GJ		GJ signaling enhances production of cytokines in cancer cells and endothelin in astrocytes, which in turn upregulate AKT/MAPK signaling in breast cancer (MDA-MB-231) and lung cancer (H226) cells to protect from cytotoxicity of chemotherapeutic drugs	[30]
Breast cancer–Astrocyte, Lung cancer–Astrocyte	GJ	cGAMP	cGAMP from metastasized cancer cells to astrocytes induces STING signaling in astrocytes, which in turn stimulate cancer metastasis	[31]
Microglia–Retinal cerebral endothelial cell	HCs		Microgila secretes basigin via activation of PI3K/Akt signaling or IGF signaling that in turn promote angiogenesis in cerebral endothelial cell	[32]

Tumor suppressive effect of Cx43 is in green while those in pink indicates Cx43 works in a tumor promotive manner. Although Table 1 contains Cx43 reports regarding various cell combinations not limited to CNS, it is generally accepted that the fundamental role of connexin is the same in peripheral tissues and the CNS. Bcl2-associated protein X, Bax; BMSCs, bone mallow stroma cells; cGAMP, 2′3′-cyclic GMP-AMP; CNS, central nervous system; DC, dendritic cells; GJ, gap junction; HCs, hemichannels; HMEC, human micro vascular cerebral endothelial cells; Interleukin 1 beta, IL-1β; JNK, c-Jun N-terminal kinase; Src, Proto-oncogene tyrosine-protein kinase Src; TNF-α, Tumor necrosis factor alpha.