Inhibitory Effect Of ?-Catenin (583-664aa) Fragment On Transcriptional Activity Of FOXM1

As an important molecule of Wnt signaling pathway,?-Catenin is one of the earliest found adhesion molecules.Its molecular weight is 90 KD,mainly located in the cell membrane,a small amount of free in the cytoplasm.About 10% of cancers have been detected with high expression,which has attracted wide attention.The final signal of classical Wnt signaling pathway is formed by the gene expression products of ?-Catenin and TCF.When this signaling pathway is activated,?-Catenin accumulates in the cytoplasm and then enters the nucleus,binding to TCF transcription factors bound to DNA.Its C-terminal is a strong trans-activating domain,which can bind to a variety of substances and activate or inhibit them.Since it was confirmed in 2011 that ?-Catenin can bind to FOXM1,more and more papers have reported that the combination of ?-Catenin and FOXM1 plays an important role in the occurrence of cancer.With the development of cancer research,people find that FOXM1 has high expression in many kinds of cancer.Inhibition of FOXM1 expression can effectively inhibit the process of proliferation,dryness,epithelial-mesenchymal transformation,apoptosis and so on.Therefore,FOXM1 may become an effective target for the development of cancer therapy drugs.FOX(Forkhead box)gene is an important gene widely existing in animals and fungi.At present,more than 100 species have been identified.The transcription factor protein family contains a highly conserved DNA binding region of about 100 amino acids,the Forkhead domain.Forkhead box M1(Forkhead box M1)is an important member of the Fox protein family and has been proved to be highly expressed in many tumors.A large number of studies have shown that FOXM1 is related to the proliferation,migration,anti-apoptosis and chemotherapy resistance of tumors.FOXM1 promotes the proliferation of cancer cells by accelerating cell cycle and inhibiting cell apoptosis.Cell division cycle 25(CDC25)belongs to the bispecific phosphatase family,which can dephosphorylate phosphorylated serine and threonine.In humans,the CDC25 bispecific phosphatase family consists of three members: CDC25 A,B and C.It regulates the cell cycle process by activating the corresponding complex.Proliferating cell nuclear antigen(PCNA)is named for its presence in the proliferating cell nucleus.Detection of the expression of PCNA can help to determine the state of cell proliferation.In this paper,COIP and co-localization experiments confirmed that ?-Catenin(583-664aa)could bind to FOXM1 directly.CMV promoter-mediated expression plasmid of ?-Catenin(583-664aa)was used to overexpress ?-Catenin(583-664aa)in cancer cells,which could effectively inhibit the transcriptional activation of FOXM1.In MCF-7 cells,high expression of ?-Catenin(583-664aa)could down-regulate FOXM1 expression.The proliferation-related genes downstream of FOXM1 were detected.The proliferation ability of MCF-7 cells was analyzed by CCK-8 assay,cloning formation assay and flow cytometry.It is confirmed that the high expression of ?-Catenin(583-664aa)in MCF-7 cells can effectively inhibit its proliferation.Therefore,the fragment of ?-Catenin(583-664aa)has a good inhibitory effect on the transcriptional activity of FOXM1 and may become a potential protein drug for cancer therapy.