| First Author | Wang Q | Year | 2018 |
| Journal | Cancer Res | Volume | 78 |
| Issue | 12 | Pages | 3163-3175 |
| PubMed ID | 29666061 | Mgi Jnum | J:262591 |
| Mgi Id | MGI:6162411 | Doi | 10.1158/0008-5472.CAN-17-3107 |
| Citation | Wang Q, et al. (2018) Deptor Is a Novel Target of Wnt/beta-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth. Cancer Res 78(12):3163-3175 |
| abstractText | Activation of the Wnt/beta-catenin signaling pathway drives colorectal cancer growth by deregulating expression of downstream target genes, including the c-myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in colorectal cancer have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to colorectal cancer growth and metastasis. Here, we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/beta-catenin/c-Myc signaling in colorectal cancer cells. Inhibition of Wnt/beta-catenin or knockdown of c-Myc decreased, while activation of Wnt/beta-catenin or overexpression of c-Myc increased the expression of Deptor. c-Myc bound the promoter of Deptor and transcriptionally regulated Deptor expression. Inhibition of Wnt/beta-catenin/c-Myc signaling increased mTOR activation, and the combination of Wnt and Akt/mTOR inhibitors enhanced inhibition of colorectal cancer cell growth in vitro and in vivo Deptor expression was increased in colorectal cancer cells; knockdown of Deptor induced differentiation, decreased expression of B lymphoma Mo-MLV insertion region 1 (Bmi1), and decreased proliferation in colorectal cancer cell lines and primary human colorectal cancer cells. Importantly, our work identifies Deptor as a downstream target of the Wnt/beta-catenin/c-Myc signaling pathway, acting as a tumor promoter in colorectal cancer cells. Moreover, we provide a molecular basis for the synergistic combination of Wnt and mTOR inhibitors in treating colorectal cancer with elevated c-Myc.Significance: The mTOR inhibitor DEPTOR acts as a tumor promoter and could be a potential therapeutic target in colorectal cancer. Cancer Res; 78(12); 3163-75. (c)2018 AACR. |
