Catenin. Additionally, the overexpression of IQUB substantially improved the activity of Wntcatenin signaling pathway, even though IQUB knockdown significantly decreased the activity of Wntcatenin signaling pathway by TOPFOPflash assay. In conclusion, our study indicated that IQUB promoted the proliferation and migration of breast cancer cells by means of activating Wntcatenin signaling pathway. Nevertheless, there had been no studies explored the mechanism of IQUB regulating Wntcatenin signaling pathway. For the Wntcatenin signaling pathway, Wnt protein interacted using the Frizzled household receptor on the cell membrane, and then disheveled (DVL) protein in the cytoplasm received biological signals and continued to transmit, resulting in the accumulation of catenin inside the cytoplasm,LI et aL.FIGUREIQUB promotes proliferation and migration of breast cancer cells through AktGSK3catenin signaling pathway. A, Akt inhibitor MK2206 (0.1 molL) reduces impact of IQUB overexpression on promoting proliferation of MDAMB231 cells. B, Akt inhibitor MK2206 (0.1 molL) reduces impact of IQUB overexpression on advertising migration of MDAMB231 cells. C, Functioning model for the regulation of proliferation and migration of breast cancer cells by IQUB via AktGSK3catenin signaling pathway. The upregulated IQUB promotes proliferation and migration of breast cancer cells via activating AktGSK3catenin signaling pathway. P .01, P .sooner or later top catenin to enter the nucleus to interact with TCFLEF loved ones of proteins to type a transcriptional activation complex, ultimately activated a series of cell proliferation and migrationrelated target genes.29 Axin, APC, GSK3, and CK1 inside the cytoplasm formed degradation complexes when Wnt signaling pathway was inactivated.When the degradation complex interacted with catenin, catenin was phosphorylated and ubiquitinated, followed by degradation by intracellular proteasomes.14 The impact of degradation complicated mainly depended on the kinase activity of GSK3. Phosphorylation of catenin at Ser33 and Ser37 by GSK3 could ultimately leading to catenin degradation,LI et aL.ORCID Kai Li http:orcid.org000000020318and thereby inhibited Wntcatenin signaling pathway.30 Hence, decreased kinase activity of GSK3 will activate Wntcatenin signaling pathway.18 It was known that phosphorylation of GSK3 at Ser9 would bring about inactivation of GSK3. Furthermore, GSK3 was a phosphorylation substrate of Akt.17 Activation of Akt promoted the phosphorylation of GSK3 at Ser9, which in turn inhibited the degradation of catenin and activated Wntcatenin signaling pathway.31 In this study, we identified that IQUB overexpression increased the expression of pAkt, pGSK3, and inhibited pcatenin, whereas IQUB knockdown showed the opposite impact. Take all these benefits into consideration, IQUB could activate Wnt catenin signaling by activating AktGSK3 pathway. Additionally, we found that Licl, a GSK3 inhibitor, could drastically reverse the inhibitory BCTC Autophagy effect of IQUB knockdown on the expression of catenin and activity of Wntcatenin signaling pathway. In addition, IQUB overexpression showed a similar impact with Licl, which both acted as GSK3 inhibitor to activate Wntcatenin signaling pathway. Furthermore, Akt inhibitor MK2206 could substantially inhibit the impact of IQUB overexpression on upregulating pGSK3 and catenin and activating Wntcatenin signaling pathway. These results indicated that IQUB could activate Wntcatenin signaling pathway by means of AktGSK3 pathway. Moreover, it was intriguing to not.
