文献类型：期刊文献

英文题名：RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

作者：Wang, Tao[1,2];Zhang, Wei-Sheng[2];Wang, Zheng-Xia[3];Wu, Zhi-Wei[4];Du, Bin-Bin[2];Li, Lai-Yuan[2];Chen, Yi-Feng[2];Yang, Xiong-Fei[2];Hao, Xiang-Yong[5];Guo, Tian-Kang[1,5]

第一作者：Wang, Tao

通信作者：Yang, XF[1];Hao, XY[2];Guo, TK[2]

机构：[1]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]Gansu Prov Peoples Hosp, Dept Colorectal Surg, 204 Donggang West Rd, Lanzhou, Gansu, Peoples R China;[3]Lanzhou Univ, Hosp 2, Dept Otolaryngol, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Sch Preclin Med, Lanzhou, Gansu, Peoples R China;[5]Gansu Prov Peoples Hosp, Dept Gen Surg, 204 Donggang West Rd, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Peoples Hosp, Dept Colorectal Surg, 204 Donggang West Rd, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Prov Peoples Hosp, Dept Gen Surg, 204 Donggang West Rd, Lanzhou, Gansu, Peoples R China.

年份：2020

卷号：9

期号：4

起止页码：1529

外文期刊名：CANCER MEDICINE

收录：;Scopus(收录号：2-s2.0-85077897671);WOS:【SCI-EXPANDED(收录号:WOS:000504770400001)】；

基金：The Nature Science Foundation for Young Scientists & Technology Planning Project of Gansu Province (18JR3RA058) and The Research Projects of Gansu Provincial people's Hospital (19SYPYB-6, 19SYPYB-7, 18GSSY4-2, 18GSSY3-1).

语种：英文

外文关键词：colorectal cancer; cyclinA2; mTORC1; proliferation; RAPTOR; URB1

摘要：Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.