| Breast cancer is the top killer among female cancers with the first annual incidence rate and the second fatality rate.Clinical tumor markers CA153 and CA125 are commonly used to detect them.MUC16,a precursor of the clinical tumor marker CA125,is highly expressed in breast and ovarian cancers.In our previous published paper,we found that upregulation of MUC16 can promote the expression of β-catenin protein,and activate downstream genes of the Wnt signaling pathway,therefore to promote cell proliferation and migration of tumor cells.Cby is a suppressor of the Wnt signaling pathway.Recent studies showed that this molecule could inhibitβ-catenin expression and transport it out of the nucleus,leading to a down-regulation of Wnt signaling pathway.The Wnt signaling pathway is involved in the regulation of cell proliferation,migration,homeostasis and self-renewal.Abnormally activated Wnt signaling pathway is closely related to the occurrence and development of tumor cells.P-catenin play an important role in the Wnt signaling pathway.Accumulation of P-catenin in the nucleus can activate the expression of Wnt signaling pathway downstream genes such as c-Myc and CyclinD.Our study found that Cby can inhibit the proliferation of MUC16 positive breast cancer cells.The relevant mechanism is that,on the one hand,in breast cancer cells,over-expression of Cby can inhibit expression of P-catenin protein;on the other hand,Cby can compete to MUC16 for binding to p-catenin,which leads to inhibit the nuclear accumulation of β-catenin protein,and inactivate downstream genes of Wnt signaling pathway.Furthermore,we also demonstrated that MUC16 could stabilizeβ-catenin,and interact with it in the nucleus. |
