TRIP6属于Zyxin家族成员，其在结直肠癌中的作用及调控机制尚不清楚。前期我们发现TRIP6在结直肠癌中存在普遍的低表达。体内外的实验表明，人为地改变TRIP6的表达可显著影响结直肠癌细胞的生长、侵袭和转移。进一步研究发现，TRIP6可通过与LATS1的相互作用，增强LATS1对YAP的磷酸化修饰及其癌基因活性的调控，这是TRIP6调控结直肠癌生长及转移的重要分子基础；同时，LATS1对TRIP6的磷酸化修饰存在一定的影响。基于此，我们提出TRIP6与Hippo-YAP信号之间的交互作用构成一种新型的调控机制，并参与到结直肠癌的发生发展。本研究拟应用基于CRISPR/Cas9技术构建的TRIP6基因敲除小鼠、结直肠癌相关细胞系及结直肠癌临床组织标本从整体动物模型、细胞模型及临床标本等方面明确TRIP6与Hippo-YAP信号转导之间的交互调控，并探讨它们在结直肠癌发生及转移中的作用。

TRIP6 (thyroid hormone receptor interacting protein 6) belongs to a member of the zyxin family. However, the role of TRIP6 in colorectal cancer (CRC), and the mechanisms involved remain largely elusive. Using human CRC tissues, we found that TRIP6 was downregulated in tumors. Our in vitro and in vivo studies revealed that alteration of TRIP6 expression significantly affected the growth and metastasis of CRC. Mechanistically, TRIP6 controlled Hippo-YAP signalling to inhibit CRC development, acting to interact with LATS1 and regulate the phosphorylation and oncogenic activity of YAP. On the other hand, the phosphorylation of TRIP6 could be regulated by LATS1. Based on these findings, we here hypothesize that the crosstalk between TRIP6 and Hippo-YAP signalling contributes to colorectal tumorigenesis and metastasis. We will aim to study the regulatory mechanism of TRIP6/Hippo-YAP signalling using CRISPR/Cas9-based TRIP6 knockout mice, CRC cell lines and clinical CRC tissues, and uncover the potential role and clinical signification of TRIP6/Hippo-YAP signalling axis in colorectal tumorigenesis and metastasis.