title: DEPTOR expression negatively correlates with mTORC1 activity and tumor progression in colorectal cancer.
abstract: 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.
authors: The Clinical Research Center for Colorectal Tumor, The Third Affiliated Hospital of Kunming Medical University, Kunming, China E-mail : baixc15@smu.edu.cn.
authors: Er-Yong
authors: EY
authors: Lai
authors: Zhen-Guo
authors: ZG
authors: Chen
authors: Xuan
authors: X
authors: Zhou
authors: Xiao-Rong
authors: XR
authors: Fan
authors: Hua
authors: H
authors: Wang
authors: Ping-Lin
authors: PL
authors: Lai
authors: Yong-Chun
authors: YC
authors: Su
authors: Bai-Yu
authors: BY
authors: Zhang
authors: Xiao-Chun
authors: XC
authors: Bai
authors: Yun-Feng
authors: YF
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C556139:DEPTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases