Tumor dissemination and metastasis are the leading causes of death in endometrial cancer. Acquired expression of certain Trk family members in more info various cancer types can be a good prognostic indicator. However, elevated expression of TrkB has been associated with poor survival of breast cancer patients. A role for TrkB in preventing anoikis was revealed in an unbiased screen of rat intestinal epithelial cells and TrkB was shown to induce a profound morphological change in which the expression of epithelial Inhibitors,Modulators,Libraries markers was reduced and the expression of mesenchymal markers was enhanced. TrkB is proposed to function as a key regulator of oncogenesis and tumor progression in a variety of human cancers, including lung, breast, pancreatic, stomach, colon, prostate, and ovarian cancer.

In our previous study, Inhibitors,Modulators,Libraries we confirmed that stimulation with brain derived neurotrophic factor, a natural ligand for TrkB, enhances TrkB mediated endo metrial carcinoma cell survival. The kinase activity of TrkB contributes to endometrial carcinoma progression by inhibiting anoikis and promoting EMT. In the present study, TrkB mRNA appeared to have no obvious change between endometrial carcinoma and normal tissues while TrkB protein levels varied markedly between endometrial carcinoma and normal tissues. This observation led us to hypothesize that TrkB expression is upregulated via a posttranscriptional mechanism in endometrial carcin oma progression. miRNA Inhibitors,Modulators,Libraries profiling analysis. We provide evidence that miR 204 5p, which acts as a potent tumor growth and metastasis suppressor both in vitro and in vivo, is somatic ally lost in human endometrial carcinoma.

The finding that miR 204 5p is downregulated in endometrial carcinoma is intriguing, as decreased miR 204 5p levels Inhibitors,Modulators,Libraries have been reported in several types of solid tumors, and suggests that Inhibitors,Modulators,Libraries loss of miR 204 5p may be a common event in tumorigenesis. STAT3 is classified as a proto oncogenic transcription factor, and constitutive activation of STAT3 has been frequently detected in various types of human cancers including endometrial carcinoma. We and others have shown that as a receptor tyrosine kinase, TrkB acti vates downstream signaling cascades that ultimately induce cellular proliferation through the STAT3 signaling pathways. To date, many studies have focused on miRNAs and their regulated targets, but few studies have investigated how miRNA expression is controlled transcriptionally.

In this study, we show that reduction of miR 204 correlates with phosphorylation of STAT3, which directly binds to the regulatory sites of its host gene, TRPM3, Brefeldin A side effects suggesting a regulatory mechanism for TrkB in controlling miR 204 levels through STAT3 activation. Interestingly, TRPM3 is a member of the transient receptor potential melastatin family, which has also been reported to be associ ated with cancer progression.