Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.
Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.
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DOI：
10.1186/1476-4598-9-57
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发表时间：
2010-03-12
期刊：
影响因子：
37.3
通讯作者：
Dormond O
中科院分区：
文献类型：
--
作者：
Roulin D;Cerantola Y;Dormond-Meuwly A;Demartines N;Dormond O
哺乳动物雷帕霉素靶蛋白（mTOR）存在于两种功能不同的复合物中，mTORC 1和mTORC 2在肿瘤生长中起重要作用。尽管mTORC1在这一过程中的作用已得到很好的表征，但对mTORC2在癌症进展中的功能知之甚少。在这项研究中，我们探讨了mTORC2在结肠癌中的具体作用，使用短发夹RNA表达系统沉默mTORC2相关蛋白rictor。我们发现在HT 29和LS 174T结肠癌细胞中Rictor的下调显著降低了细胞增殖。通过细胞周期分析观察到，rictor的敲除也导致G1期阻滞。我们进一步观察到，缺乏Rictor的LS 174 T细胞在裸鼠异种移植模型中不能形成肿瘤。综上所述，这些结果表明mT0RC 2的抑制减少了体外结肠癌细胞增殖和体内肿瘤异种移植物形成。他们还表明，特异性靶向mTORC 2可能为结直肠癌提供一种新的治疗策略。
The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes, mTORC1 and mTORC2 plays an important role in tumor growth. Whereas the role of mTORC1 has been well characterized in this process, little is known about the functions of mTORC2 in cancer progression. In this study, we explored the specific role of mTORC2 in colon cancer using a short hairpin RNA expression system to silence the mTORC2-associated protein rictor. We found that downregulation of rictor in HT29 and LS174T colon cancer cells significantly reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice xenograft model. Taken together, these results show that the inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting mTORC2 may provide a novel treatment strategy for colorectal cancer.
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DOI：
10.1073/pnas.0810715105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Rychahou, Piotr G.;Kang, JungHee;Evers, B. Mark
通讯作者：
Evers, B. Mark
影响因子：
3.7
作者：
Zhang, Yan-Jie;Dai, Qiang;Fang, Jing-Yuan
通讯作者：
Fang, Jing-Yuan
影响因子：
16
作者：
Sarbassov, DD;Ali, SM;Sabatini, DM
通讯作者：
Sabatini, DM
影响因子：
9.8
作者：
Feldman ME;Apsel B;Uotila A;Loewith R;Knight ZA;Ruggero D;Shokat KM
通讯作者：
Shokat KM
影响因子：
11.2
作者：
Yu, Ker;Toral-Barza, Lourdes;Zask, Arie
通讯作者：
Zask, Arie