Regulation of MLK3 by LATS

摘要 混合谱系激酶3和4是调节MAPK的丝裂原活化蛋白激酶(MAPK) 信号通路，并介导信号从细胞表面受体到 原子核。MLK3和MLK4在卵巢癌的侵袭和迁移中具有重要作用 乳腺癌细胞。上皮间充质转化(EMT)是上皮细胞 细胞失去细胞极性和粘附性，获得迁移和侵袭性 间充质细胞的特性。EMT的异常激活可促进细胞 转化和癌症进展。了解EMT是如何监管的对于 开发新的癌症治疗方法。由于它们在细胞转化中的作用，我们 推测MLK3和MLK4可能是卵巢EMT过程的重要调节因子 癌细胞。利用siRNA敲除SKOV3中MLK3和MLK4的初步发现 卵巢癌细胞提示MLK3或MLK4的缺失会影响EMT标志物E- 钙粘附素和波形蛋白。我们认为MLK3和MLK4是EMT的重要调节器，并且 当在卵巢癌细胞中异常调节时，促进EMT进展、侵袭和 肿瘤发生学。在本研究中，我们将研究MLK3和MLK4的作用机制 调节关键EMT标志物的表达，控制卵巢癌球体的形成和 入侵。

Abstract Mixed lineage kinase 3 and 4 are mitogen-activated protein kinases (MAPKs) that regulate MAPK signaling pathways, and mediate transmission of signals from cell surface receptors to the nucleus. MLK3 and MLK4 have important functions in invasion and migration of ovarian and breast cancer cells. Epithelial mesenchymal transition (EMT) is the process by which epithelial cells lose cell polarity and adhesion properties and acquire the migratory and invasive characteristics of mesenchymal cells. Aberrant activation of EMT can contribute to cell transformation and cancer progression. Understanding how EMT is regulated is important for development of new cancer treatments. Due to their functions in cellular transformation, we hypothesized that MLK3 and MLK4 could be important regulators of the EMT process in ovarian cancer cells. Our preliminary findings using siRNA knockdown of MLK3 and MLK4 in SKOV3 ovarian cancer cells indicate that loss of MLK3 or MLK4 affects the levels of EMT markers, E- cadherin and vimentin. We propose that MLK3 and MLK4 are important modulators of EMT, and when aberrantly regulated in ovarian cancer cells, promote EMT progression, invasion and tumorigenesis. In the current study, we will investigate the mechanisms by which MLK3 and MLK4 regulate the expression of key EMT markers, and control ovarian cancer spheroid formation and invasion.