Overexpression of SOX18 correlates with accelerated cell growth and poor prognosis in human pancreatic ductal adenocarcinoma

Biochem Biophys Res Commun. 2016 Oct 21;479(3):510-516. doi: 10.1016/j.bbrc.2016.09.099. Epub 2016 Sep 20.

Abstract

Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy.

Keywords: Cell growth; Invasion; Migration; Pancreatic ductal adenocarcinoma (PDAC); Prognosis; SOX18.

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism
  • SOXF Transcription Factors / metabolism*
  • Transfection

Substances

  • CCND1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • SOX18 protein, human
  • SOXF Transcription Factors
  • Cyclin D1
  • MMP7 protein, human
  • Matrix Metalloproteinase 7