FAM134B属于序列相似134家族，申请人前期研究发现FAM134B通过激活AKT通路促进肝癌的进展和转移，然而FAM134B的上游调控目前还不清楚。申请人质谱检测发现，CKAP4是FAM134B的结合蛋白。而且CKAP4能够上调FAM134B的表达，但对其mRNA水平无影响。敲减CKAP4引起的FAM134B下调可以被蛋白酶体抑制剂回复。同时我们还发现CKAP4在肝癌组织中高表达，功能学实验证明CKAP4促进肝癌细胞增殖，迁移和侵袭。据此我们提出科学假设：CKAP4直接结合FAM134B，并通过与E3泛素连接酶竞争性结合FAM134B保护其免受泛素化降解（或促进去泛素化酶对FAM134B的去泛素化），从而激活AKT通路促进肝癌的进展与转移。本课题有望初步阐明CKAP4-FAM134B-p-AKT通路促进肝癌增殖和转移的全新分子机制，为肝癌转移的治疗提供新的靶点。

FAM134B belongs to the family of similar 134 sequences. The applicant's previous research found that FAM134B promoted the progression and metastasis of HCC by activating the AKT pathway. However, the upstream regulation of FAM134B is unclear. The mass spectrometry revealed that CKAP4 is a binding protein of FAM134B. Moreover, CKAP4 can up-regulate the protein expression of FAM134B, but has no effect on its mRNA level. Down-regulation of FAM134B caused by knockdown of CKAP4 can be restored by proteasome inhibitors. At the same time, we also found that CKAP4 was highly expressed in HCC tissues. Functional experiments have proven that CKAP4 promoted the proliferation, migration and invasion of HCC cells. Based on this, we propose a scientific hypothesis: CKAP4 directly binds FAM134B, and protects it from ubiquitination through competitive binding with E3 ubiquitin ligase (or promotes deubiquitination of FAM134B by deubiquitinase), thereby activation of AKT pathway to promote the progression and metastasis of HCC. This project is expected to clarify the new molecular mechanism of CKAP4-FAM134B-p-AKT pathway to promote the proliferation and metastasis of HCC, and provides new targets for the treatment of liver cancer metastasis.