Abnormal Differentiation in Cancer Cells and Intracellular Signaling

在这项研究中，我们重点研究了与肿瘤发生有关的许多细胞内信号通路中的Wnt信号。我们从分化和极性的角度分析了Wnt信号异常导致肿瘤发生的分子机制。澄清了以下几点。(1)纯化了Wnt蛋白，并阐明了其翻译后修饰的作用。(2)受体介导的内吞途径在多种Wnt信号的选择性激活中发挥作用。(3)Wnt5a信号调节细胞迁移和细胞极性。(4)Wnt5a信号异常与肿瘤的侵袭性有关。(5)鉴定了与蛋白激酶GSK-3结合的新蛋白，它们参与了微管动力学和局部黏附的调节。(6)DVL调节有丝分裂中的纺锤体动力学和纺锤体组装动力学。

In this study we focused in Wnt signaling among many intracellular signaling pathways involved in tumorigenesis. We analyzed the molecular mechanisms of tumorigenesis by abnormality in Wnt signaling in the light of differentiation and polarity. The following points are clarified. (1) Wnt proteins were purified and the roles of their post-translational modifications were clarified. (2) Receptor-mediated endocytic routes played a role in the selective activation of multiple Wnt signaling. (3) Wnt5a signaling regulated cell migration and cell polarity. (4) Abnormalities in Wnt5a signaling were involved in aggressiveness of human cancer. (5) Novel binding proteins to GSK-3, a protein kinase, were identified, and they were involved in the regulation of microtubule dynamics and focal adhesion. (6) Dvl regulated spindle dynamics and spindle assemble dynamics in mitosis.