PMID- 24969890 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20220321 IS - 2476-762X (Electronic) IS - 1513-7368 (Linking) VI - 15 IP - 11 DP - 2014 TI - DEPTOR expression negatively correlates with mTORC1 activity and tumor progression in colorectal cancer. PG - 4589-94 AB - The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC. FAU - Lai, Er-Yong AU - Lai EY AD - The Clinical Research Center for Colorectal Tumor, The Third Affiliated Hospital of Kunming Medical University, Kunming, China E-mail : baixc15@smu.edu.cn. FAU - Chen, Zhen-Guo AU - Chen ZG FAU - Zhou, Xuan AU - Zhou X FAU - Fan, Xiao-Rong AU - Fan XR FAU - Wang, Hua AU - Wang H FAU - Lai, Ping-Lin AU - Lai PL FAU - Su, Yong-Chun AU - Su YC FAU - Zhang, Bai-Yu AU - Zhang BY FAU - Bai, Xiao-Chun AU - Bai XC FAU - Li, Yun-Feng AU - Li YF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Thailand TA - Asian Pac J Cancer Prev JT - Asian Pacific journal of cancer prevention : APJCP JID - 101130625 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Multiprotein Complexes) RN - EC 2.7.1.1 (DEPTOR protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Differentiation/genetics MH - Colorectal Neoplasms/*genetics/metabolism/*pathology MH - Disease Progression MH - Disease-Free Survival MH - Down-Regulation/genetics MH - Female MH - Humans MH - Intracellular Signaling Peptides and Proteins/*genetics MH - Lymphatic Metastasis/genetics/pathology MH - Male MH - Mechanistic Target of Rapamycin Complex 1 MH - Middle Aged MH - Multiprotein Complexes/*genetics/*metabolism MH - Neoplasm Invasiveness/genetics/pathology MH - Prognosis MH - TOR Serine-Threonine Kinases/*genetics/*metabolism MH - Up-Regulation/genetics MH - Young Adult EDAT- 2014/06/28 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/06/28 06:00 PHST- 2014/06/28 06:00 [entrez] PHST- 2014/06/28 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - 10.7314/apjcp.2014.15.11.4589 [doi] PST - ppublish SO - Asian Pac J Cancer Prev. 2014;15(11):4589-94. doi: 10.7314/apjcp.2014.15.11.4589.