Connexin 43 trafficking and regulation of gap junctional intercellular communication alters ovarian cancer cell migration and tumorigenesis. 2023

Vaishali Mulchandani, and Anurag Banerjee, and Arunima Vijaya Vadlamannati, and Saurav Kumar, and Jayasri Das Sarma
Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India.

Ovarian cancer persists to be the most lethal gynecological malignancy, demanding rigorous treatments involving radio-chemotherapy that trigger toxicity and consequently mortality among patients. An improved understanding of the disease progression may pioneer curative therapies. Mouse epithelial ovarian cancer cell lines, ID8 and ID8-VEGF (overexpressing VEGF) were intraperitoneally injected in C57BL/6 female mice to develop a Syngeneic Ovarian cancer mouse model. It was observed that ID8-VEGF cells were able to induce aggressive tumor growth in mice compared to ID8 cells. Furthermore, results of the current in vitro study comparing ID8 and ID8-VEGF demonstrated that highly tumorigenic ID8-VEGF had reduced gap junctional intercellular communication (GJIC) due to intracellular Connexin 43 (Cx43) expression. Additionally, ID8 cells with reduced tumorigenic capability expressed significant GJIC. Furthermore, loss of GJIC in ID8-VEGF cells induced shorter tunneling nanotube formations, while ID8 cells develops longer tunneling nanotube to maintain cellular crosstalk. The administration of a pharmacological drug 4-phenylbutyrate (4PBA) ensured the restoration of GJIC in both the ovarian cancer cell lines. Additionally, 4PBA treatment significantly inhibited the migration of ovarian cancer cell lines and tumor formation in ovarian cancer mice models. In summary, the 4PBA-mediated restoration of GJIC suppressed migration (in vitro) and tumorigenesis (in vivo) of ovarian cancer cells. The present study suggests that Cx43 assembled GJIC and its supportive signaling pathways are a prospective target for restricting ovarian cancer progression.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018031 Connexin 43 A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain. Cx43,Connexin43

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