The Study Of Effects Of The Sugar Chains Of The Tumor Cell Surface On Gap Junction Intercellular Communication And Its Mechanism

Gap junction intercellular communication (GJIC), is a pathway of the direct cell to cell communication through the gap junctions(GJs) of the neighboring cells needless of intercellular substance. It can transfer the small molecules less than 1-2KDa via this pathway, for example metal ions, second messenger and other small molecule metabolites and so on.In cancer, loss of these types of cell to cell interactions has been shown to facilitate tumorigenesis. It is supposed that restoration of GJIC function of the tumor cells or between the tumor cells and the corresponding normal cells can normalize phaenotype. These studies strongly suggest that the normal GJIC serves a tumor suppressor role. It is possible that the research of GJIC will be potential anti-oncogenic targets for chemoprevention and/or chemotherapy.The aberrant excessive glycoprotein and glycolipid on the cellular membrane is shown in tumor cells. The change of the glycosyltransferase often induces structural changes, for example N-linked glycosylation of Asn, O-linked glycan of Ser and Thr, Ser-linked GAGs, and glycolipids.of lipid. Sialic acid is an important part of glycoprotein and glycolipid on the cellular membrane. Its metabolism plays a role in tumor proliferation, invasion and metastasis. Sialic acid on tumor cell surface is obviously expressed higher than normal cells. For example it is expressed in cervix uteri cancer cells but not normal cervix uteri cells. It is highly expressed in patients'cervix uteri cancer tissues which are in low cell differentiation and later clinical stage.Many articles reported that GJIC was lower in tumor cells than normal. One possible reason is low expression level of Cx43, the other is that Cx43 can't form correct and complete channels which are related with mass abnormal glycons on the tumor cell surface. It's thought that the mass abnormal glycons hinder the formation of GJIC channels. At present, It is confirmed that suppressing glycosylation by tunicamycin makes for opening of GJIC channels. We suppose that the abnormal excessive sialic acid on the tumor cell surface also influences GJIC by this way. In the research of N-linked carbohydrate, it is discovered thatβ-1,6-N-Acetylglucosaminyltransferase V (GnT-V) also induces Tumor, but its function in GJIC has not reported, so it is my another target, too.Due to the lack of potential glycosylation sites in their exacellular loops, Cx43 is unlikely to be affected directly because of the reduction of sialic acid andβ-1,6 branches. Therefore, a reduction of carbohydrates from other cell surface proteins other than Cx43 is a more likely cause for the observed increase in communication. Its reduction influences the formation and opening of the channels through influencing the expression and distribution of Cx43 and its related proteins.Recently we study the sugar chains via the interference of chemical materials or molecular bio-technology. In this article I will observe the influence on the GJIC of the aberrant excessive glycons on the cellular membrane, depending on the chemical materials (tunicamycin, TM / neuraminidase) and iRNA technology through inhibition of the glycosylation, and preliminarily reveal its molecular mechanism that how the aberrant excessive sialic acid on the cell surface inhibits GJIC.GJIC of HeLa which is detected by both SLDT and FRAP is increased after removal ofα2-3 andα2-6 sialic acid by neuraminidase or silencing of the GnT-V by iRNA technology. However the expression and phosphorylation of Cx43 are not obviously changed after treatment, but the distribution of Cx43 is changed and the quantity of Cx43 in the gap junctional plaques is increased. The experiment also finds that the expression of two Cx43 related proteins N-cadherin and ZO-1 is not obviously changed, but the co-localization with Cx43 both increase, and GJIC is enhanced noticeably. This is maybe caused by the reduction of the stereospecific blockade because of the removel of of the glycoprotein on the cell surface..The study of this article is helpful to elucidate the biological function of saccharide especially sialic acid andβ-1,6 branches on tumor cell surface, and to provide theory on drug research and development arming at tumor GJIC and abnormal glycons.