They no longer require attachments for their survival and thus achieve anoikis resistance. Twist plays a critical role in breast cancer metastasis. Furthermore, high Twist expression in D-Pantothenic acid sodium infiltrative EC affects patient survival, though the mechanism of EMT in EC Mepiroxol remains unclear. Results from our study support high levels of Twist in EC, which are significantly associated with TrkB expression. Furthermore, we show that levels of Twist expression are modulated by TrkB and are required for TrkB-induced EMT transformation and tumorigenesis in vitro. Notably, in anchorage-independent culture, we found that both TrkB and Twist were expressed in survival cell spheroids, and many EMT-related genes were differentially expressed compared to adherent cells, which are hallmarks of the oncogenic EMT being required for anoikis resistance. Peritoneal dissemination of EC cells is a multistep process consisting of invasion into the serosa from the uterus, detachment from the primary site, movement into the peritoneal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space, and proliferation. From our in vivo experiments, we discovered that the TrkB knockdown significantly inhibited the establishment of intraperitoneal disseminated tumors. A constitutive “cadherin switch” and apoptosis shift were also detected in paraffin-embedded sections of mouse tumors, which are consistent with the in vitro results. Mechanistically, Trks are receptor tyrosine kinases activated by neurotrophins and other growth factors. TrkA, TrkB and TrkC are the preferred receptors for the neurotrophins NGF, BDNF and neurotrophin-3, respectively. When stimulated by BDNF ligand, TrkB induces the activation of various downstream signaling pathways including Akt, Src, or MAPK resulting in cell proliferation, and apoptosis resistance in models of human cancer. In the present study, we found that both BDNF and TrkB are over-expressed in human endometrial carcinoma specimens. In vitro experiments verified that BDNF enhances cell proliferation and survival. In addition, the migratory and invasive properties of EC are mediated by a BDNF-TrkB signaling cascade in Ishikawa and RL95-2 cells. After the discovery of the involvement of the BDNF/TrkB cascade in cancer biology, it is appreciated that the inhibition of TrkB activity might be beneficial in a clinical oncology setting. Previous studies have demonstrated 
a key role for BDNF-TrkB signaling in modulating the response to cytotoxic agents, and modulation of TrkB expression enhanced the sensitivity of cells to cis-Diamminedichloroplatinum Cisplatin in head and neck squamous cell carcinoma. Recently, It was reported Trk inhibitor K252a inhibited cell growth and induced apoptotic cell death in uterine leiomyosarcoma.Therefore, further studies are needed to explore the development of small-molecule compounds that act as TrkB antagonists, or monoclonal antibodies against either BDNF or TrkB, as promising novel therapies for the treatment of endometrial carcinoma. Our findings provide new insights into biological mechanisms of EC and establish TrkB as a potential target for future therapies for this disease. The aetiology of PE is not completely understood, but it is generally considered that disturbed interactions between the invading trophoblasts and maternal cells causing defective trophoblast invasion are important pathophysiological events. The subsequent impaired spiral artery remodelling and reduced placental perfusion is proposed to create oxidative stress and a release of inflammatory factors into the maternal circulation, causing overt PE. Gene expression analyses may provide further insight in mechanisms of disease and function as preventive, predictive or therapeutic measures.