结直肠癌进展的分子机制尚不明确，靶向治疗效果有限。数据库检索发现端粒维持分子2（TELO2）在结直肠癌中表达高；本课题组预实验证实结直肠癌中TELO2表达较正常组织高，低表达可阻滞细胞周期，过表达则诱导细胞形态改变；TELO2可与雷帕霉素不敏感mTOR结合蛋白（Rictor）结合。本研究拟在结直肠癌组织、细胞中观察TELO2表达、定位，统计分析TELO2与临床病理特征的相关性；细胞功能及裸鼠转移瘤实验观察TELO2对增殖、侵袭转移的作用；免疫共沉淀及泛素化检测TELO2与Rictor细胞内的结合方式及下游信号通路；组织芯片观察TELO2和Rictor两者表达相关性及对结直肠癌预后的影响，细胞及裸鼠实验验证Rictor在TELO2诱导肿瘤进展中的作用。本课题拟证明TELO2是结直肠癌的癌基因，通过Rictor参与结直肠癌的进展，探讨结直肠癌进展的新机制，为靶向干预研究提供新的依据。

The mechanism of colorectal cancer (CRC) progression is still unknown, targeted biotherapy is approved to apply in partial mCRC and usually prolongs several months of over survival in mCRC patients. New biological target finding is still processing. GENT database showed that telomere maintenance 2 (TELO2) was highly expressed in colorectal cancer compared with normal tissue (Fig. 1). Our preliminary data verified that TELO2 was over-expressed in CRC (Fig. 2), involved in cell cycle and morphology (Fig. 3 and 4). TELO2 acted with Rapamycin-insensitive companion of mTOR (Rictor) (Fig. 5), which might be participated in CRC progression. In this proposal, qPCR, western blot, immunohistochemistry and immunofluorescence will be used to clarify the expression and location of TELO2 in CRC, statistical analysis will show the relationship between TELO2 and clinic pathology characters. WST, soft agar, flow cytometry, matrigel chamber, wound healing, and liver metastasis xenograft model in nude mice will be established to confirm the role of TELO2 during CRC progression. Furthermore, Co-IP, CHX assay and Ubiqiutination assay will be addressed to confirm binding between TELO2 and Rictor, the downstream targets of TELO2/Rictor complex will be assessed at the same time. Moreover, WST, soft agar, flow cytometry, matrigel chamber, wound healing, xenograft and liver metastasis model in nude mice will be also established to confirm the role of Rictor during TELO2 induced tumor progression. Kaplan-Meier curve will be used to analysis the relationship between expression of TELO2 and Rictor and prognosis by tissue array. This study would elucidate for the first time that TELO2 acts as an oncogene in CRC, which plays an important role in CRC progression. Rictor bind with TELO2, participate the proliferation, invasion and migration of CRC eventually. This project yields a novel opinion and method for molecular targeted treatment and prognosis of CRC.