Implication of connexin30 on the stemness of glioma: connexin30 reverses the malignant phenotype of glioma by modulating IGF-1R, CD133 and cMyc

Abstract

Gap-junctional intercellular communication (GJIC) plays a major role in the malignant growth of glioma. Although the mechanistic aspects of GJIC have been extensively studied, the role of connexins in the regulation of the malignant behavior of glioma stem cells (GSCs) remains unclear. In our previous studies, we have shown that connexin30 can interfere with the insulin-like growth factor 1 receptor (IGF-1R), which is known for self-renewal and pluripotency. Following our earlier in vitro observation, in this work, we aimed to study the consequence of this influence of Cx30 on IGF-1R by evaluating the marker of GSCs, CD133 and oncoprotein, cMyc. We strengthened our basis by examining human glioma samples of different grades as well as rat C6 xenografts (Cx30-transfected and -non-transfected C6 cells) along with the sphere formation assays in vitro. Investigation of stemness-related CD133 and cMyc in human samples and rat xenografts exhibited a reciprocal relationship between Cx30 and IGF-1R in the low and high grades (HG) of glioma. Cx30 was completely abolished in HG; levels of IGF-1R, CD133 and cMyc expression were positively correlated with HG. Cx30 transfection could attenuate the malignant burden of glioma in rat xenografts. Cx30 transfection also altered the tumor sphere formation of C6 glioma cells in vitro, an important property of GSCs, and there was a significant reduction of CD133 and cMyc expression by Cx30 both in vitro and in vivo. These factors indicate that dysfunction of Cx30 plays a crucial role in the prevention of the stemness of glioma, and the exploitation of this feature will help in the management of glioma.

Connexin 43 Loss Triggers Cell Cycle Entry and Invasion in Non-Neoplastic Breast Epithelium: A Role for Noncanonical Wnt Signaling

“…To the best of our knowledge, this is the first demonstration of an inhibitory effect for Cxs on the expression of c-Myc and cyclin D1 in the breast tissue. This effect has been reported in osteosarcoma, glioma, hepatoma, and lung carcinoma cells overexpressing Cx genes and is associated with reduced tumorigenicity [114,115,116,117]. Interestingly, T4-2 cells, the tumorigenic counterparts of S1 cells, did not show increased Wnt/β-catenin activity compared to S1 cells, suggesting the involvement of other signaling pathways.…”

Mild thermotherapy and hyperbaric oxygen enhance sensitivity of TMZ/PSi nanoparticles via decreasing the stemness in glioma

“…To further investigate the effection of TMZ/PSi combined with PTT and HBO, C6 glioma cells were used. C6 glioma cells have properties in common with glioma stem cells [33, 34]. Most of the C6 cells are cancer stem-like cells with in vitro characteristics of self-renewal [35].…”

Novel sphingomyelin biomarkers for brain glioma and associated regulation research on the PI3K/Akt signaling pathway

“…Similar results were also observed for the expression levels of proteins P-Src, P-Akt and P-S6k from the PI3K/Akt signaling pathway. Previous studies reported that the dysregulation of the IGF-1R signaling pathway results in the development of malignant gliomas (19,23,24). In addition, glioma cell senescence and apoptosis can be influenced by the activity of the PI3K/Akt signaling pathway (25,26).…”