TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2.
TELO2 induced progression of colorectal cancer by binding with RICTOR through mTORC2.
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TELO2通过mTORC2与RICTOR结合诱导结直肠癌进展
DOI：
10.3892/or.2020.7890
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发表时间：
2021-03
期刊：
影响因子：
4.2
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Guo Z;Zhang X;Zhu H;Zhong N;Luo X;Zhang Y;Tu F;Zhong J;Wang X;He J;Huang L
结直肠癌(CRC)是世界范围内常见的癌症，其治疗策略有限。CRC进展的潜在机制仍有待确定。端粒维持蛋白2(TELO2)是一种mTOR相互作用蛋白。TELO2在肿瘤进展中的作用和分子机制尚不清楚。本研究利用正常组织和肿瘤组织的基因表达数据库，结合免疫印迹分析和免疫组织化学(IHC)方法，对TELO2在大肠癌和正常组织中的表达和定位进行了研究。收集和分析了组织阵列的临床特征。采用WST-1、软琼脂、流式细胞仪、伤口愈合和侵袭实验验证TELO2在大肠癌细胞生长、细胞周期、迁移和侵袭中的作用。采用生物信息学、免疫组化和免疫沉淀法分析TELO2与RICTOR(雷帕霉素不敏感的mTOR伴侣)的相关性。收集正常细胞和去血清细胞，检测TELO2及其下游效应分子的蛋白水平。结果显示，TELO2在结直肠癌中显著上调，抑制TELO2显著抑制结直肠癌细胞的生长、细胞周期和转移。TELO2过表达与结直肠癌患者年龄、淋巴结转移和TNM分期相关。此外，在结直肠癌中，TELO2与RICTOR呈正相关，并主要通过与培养中血清的RICTOR诱导肿瘤进展。Rictor以不依赖mTOR的方式诱导血清剥夺时TELO2的降解。这些发现表明，TELO2通过RICTOR以血清依赖的方式促进肿瘤进展，这可能是结直肠癌的潜在治疗靶点。
Colorectal cancer (CRC) is a common cancer worldwide, and its treatment strategies are limited. The underlying mechanism of CRC progression remains to be determined. Telomere maintenance 2 (TELO2) is a mTOR-interacting protein. Both the role and molecular mechanism of TELO2 in cancer progression remain unknown. In this study, the gene expression database of normal and tumor tissue, in addition to western blot analysis, and immunohistochemistry (IHC) were used to determine the expression and location of TELO2 in CRC and normal tissues. Clinical features of a tissue array were collected and analyzed. WST-1, soft agar, flow cytometry, wound healing, and invasion assays were employed to verify the role of TELO2 in the growth, cell cycle, migration, and invasion of CRC cells. The correlation between TELO2 and RICTOR (rapamycin-insensitive companion of mTOR) was analyzed by bioinformatics, IHC, and immunoprecipitation. Normal and serum-deprived cells were collected to detect the protein level of TELO2 and its downstream effectors. The results revealed that TELO2 was significantly upregulated in CRC, and TELO2 inhibition significantly restrained the growth, cell cycle, and metastasis of CRC cells. TELO2 overexpression correlated with age, lymph node metastasis, and TNM stage of CRC patients. In addition, TELO2 was positively correlated with RICTOR in CRC and induced tumor progression mainly via RICTOR with serum in culture. RICTOR induced the degradation of TELO2 upon serum deprivation in an mTOR-independent manner. These findings indicate that TELO2 promotes tumor progression via RICTOR in a serum-dependent manner, which may be a potential therapeutic target for CRC.
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