title: Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Lutao
authors.initials: L
authors.lastname: Du
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wen
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
authors.forename: Guixi
authors.initials: G
authors.lastname: Zheng
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D047368:Tumor Burden / Q000235:genetics
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases