PMID- 23599173
OWN - NLM
STAT- MEDLINE
DCOM- 20131210
LR  - 20211203
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 32
IP  - 1
DP  - 2013 Jul
TI  - Sex determining region Y-box 2 inhibits the proliferation of colorectal 
      adenocarcinoma cells through the mTOR signaling pathway.
PG  - 59-66
LID - 10.3892/ijmm.2013.1354 [doi]
AB  - Sex determining region Y-box 2 (SOX2), is a high mobility group box transcription 
      factor involved in the maintenance of pluripotency and the self-renewal of 
      embryonic and neuronal stem cells, which also plays differential roles in the 
      cell proliferation of several tumors. However, its role in colorectal 
      adenocarcinoma cell proliferation and the underlying mechanisms remain unclear. 
      The mammalian target of rapamycin (mTOR) signaling pathway has recently emerged 
      as an important regulator of cell proliferation in many types of cancer. In this 
      study, we examined the effect of SOX2 on the proliferation of colorectal 
      adenocarcinoma cells and evaluated the role of the mTOR pathway in this process. 
      Our results indicated that the overexpression of SOX2 significantly inhibited the 
      proliferation of colorectal adenocarcinoma cells. Of note, mechanistic 
      investigations revealed that SOX2 inhibited the activation of the mTOR pathway in 
      HT-29 cells. We then examined the effect of SOX2 on the cell cycle, and the 
      results revealed that SOX2 downregulated cyclin D1 expression and induced G0/G1 
      arrest in the HT-29 cells. Moreover, we also analyzed the correlation between 
      SOX2 expression and patient clinicopathological characteristics in colorectal 
      adenocarcinoma tissues, as well as the level of phospho-S6 (S235/236), 
      phospho-Akt (S473) and cyclin D1. The results revealed a significant negative 
      correlation between SOX2 expression and tumor size and the levels of phospho-S6 
      (S235/236), phospho-Akt (S473) and cyclin D1. Taken together, to our knowledge, 
      our findings suggest for the first time that SOX2 suppresses colorectal 
      adenocarcinoma cell proliferation through the inhibition of the mTOR pathway.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, 
      Shandong 250012, P.R. China.
FAU - Du, Lutao
AU  - Du L
FAU - Wen, Zhihua
AU  - Wen Z
FAU - Yang, Yongmei
AU  - Yang Y
FAU - Li, Juan
AU  - Li J
FAU - Dong, Zhaogang
AU  - Dong Z
FAU - Zheng, Guixi
AU  - Zheng G
FAU - Wang, Lili
AU  - Wang L
FAU - Zhang, Xin
AU  - Zhang X
FAU - Wang, Chuanxin
AU  - Wang C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130419
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenocarcinoma/*genetics/*metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/*genetics/*metabolism/pathology
MH  - Cyclin D1/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - HT29 Cells
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - SOXB1 Transcription Factors/*genetics/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tumor Burden/genetics
EDAT- 2013/04/20 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/04/20 06:00
PHST- 2013/02/13 00:00 [received]
PHST- 2013/04/12 00:00 [accepted]
PHST- 2013/04/20 06:00 [entrez]
PHST- 2013/04/20 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.3892/ijmm.2013.1354 [doi]
PST - ppublish
SO  - Int J Mol Med. 2013 Jul;32(1):59-66. doi: 10.3892/ijmm.2013.1354. Epub 2013 Apr 
      19.