MUC16 is the largest member in mucin family members,which not only has characteristic of high glycosylation at its extracellular region,but also can shed and fall into serum,which is called CA125 as well in clinical.Expression level of CA125 is abnomally higher in tissues of ovarian cancer patients than it is normal in ovarian tissues,therefore,CA125 is usually regarded as one of the important cancer markers in the clinical for detection of epithelial ovarian cancer.In addition,MUC16 is also overexpressed in various cancers,and can interact with a number of oncogene proteins,promoting tumorigenesis.Similarly,as a classic member of the human epidermal growth factor receptor family,HER2 is highly expressed in variety of cancers,and plays an important role in promoting tumor development.In Clinical,Trastuzumab and Lapatinib were main drugs targeting to HER2,which already had gained big success,however their efficacy was often limited by patients’ tolerance to HER2 drugs.Our previous study found that MUC16 can interact with HER2,which can promote the phosphorylation and activation of HER2,increasing the tolerance of tumor cells responding to HER2 drugs.However,the specific mechanism of HER2 activation by MUC16 has not been clear yet,meanwhile the mechanism of MUC16 expression regulation is still less studied.So we supposed that HER2 signal pathway could regulate the expression of MUC16.To explore influence of HER2 signal on MUC16 expression,we performed knocking down HER2 as well as applying HER2 inhibitor to ovarian cancer cells,we found that MUC16 expression was significantly decreased;meanwhile,the expression of MUC16 was also significantly decreased after the ERK1/2 signal pathway was inhibited,indicating that HER2-ERK1/2 signal pathway can regulate MUC16 expression.To further investigate whether MUC16 expression regulated by HER2-ERK1/2 signal is mediated by a certain transcription factor,we predicted and verified that WT1 as a potential transcription factor of MUC16 could mediate the expression regulation of MUC16 by HER2-ERK1/2 signals.Meanwhile,we found that WT1 could interact with ERK1/2.Overall,our research confirmed MUC16 expression could be regulated by HER2-ERK1/2-WT1 signal axis. |