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RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1

Authors :
Zheng‐Xia Wang
Laiyuan Li
Tiankang Guo
Binbin Du
Weisheng Zhang
Xiongfei Yang
Zhi-Wei Wu
Yifeng Chen
Xiang-Yong Hao
Tao Wang
Source :
Cancer Medicine, Vol 9, Iss 4, Pp 1529-1543 (2020), Cancer Medicine
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

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.<br />Regulatory associated protein with mammalian target of rapamycin (RAPTOR) contributes to colorectal cancer proliferation and cell cycle progression through positively regulating URB1 and cyclinA2 via activating mTOR complex 1 signaling. We conclude that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for colorectal cancer.

Details

ISSN :
20457634
Volume :
9
Database :
OpenAIRE
Journal :
Cancer Medicine
Accession number :
edsair.doi.dedup.....6650a73e8303ab2cd889f69fa6fa178b