Original Article—Alimentary Tract

Journal of Gastroenterology

, Volume 49, Issue 10, pp 1378-1391

Functions and regulation of MUC13 mucin in colon cancer cells

  • Brij K. GuptaAffiliated withCancer Biology Research Center, Sanford Research/USDBasic Biomedical Science Division, Departments of Obstetrics and Gynecology, Sanford School of Medicine, The University of South Dakota
  • , Diane M. MaherAffiliated withCancer Biology Research Center, Sanford Research/USD
  • , Mara C. EbelingAffiliated withCancer Biology Research Center, Sanford Research/USD
  • , Phillip D. StephensonAffiliated withLaboratory Medicine and Pathology, Sanford School of Medicine, The University of South Dakota
  • , Susan E. PuumalaAffiliated withCenter for Health Outcomes and Prevention Research, Sanford Research
  • , Michael R. KochAffiliated withDepartment of Pathology, Sanford School of Medicine, The University of South Dakota
  • , Hiroyuki AburataniAffiliated withGenome Science Division, University of Tokyo
  • , Meena JaggiAffiliated withBasic Biomedical Science Division, Departments of Obstetrics and Gynecology, Sanford School of Medicine, The University of South DakotaDepartment of Pharmaceutical Sciences, Cancer Research Center, University of Tennessee Health Science Center
  • , Subhash C. ChauhanAffiliated withBasic Biomedical Science Division, Departments of Obstetrics and Gynecology, Sanford School of Medicine, The University of South DakotaDepartment of Pharmaceutical Sciences, Cancer Research Center, University of Tennessee Health Science Center Email author 

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Abstract

Background

MUC13 is overexpressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown.

Methods

Stable cell lines with either overexpressed or suppressed MUC13 levels were analyzed to determine cell growth, colony formation, cell migration, and cell invasion assays. The molecular mechanisms involved in MUC13 regulation were elucidated via chromatin immunoprecipitation (ChIP) and analysis of interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon cancer cells.

Results

Overexpression of MUC13 increased cell growth, colony formation, cell migration, and invasion. In concordance, MUC13 silencing decreased these tumorigenic features. Overexpression of MUC13 also modulated various cancer-associated proteins, including telomerase reverse transcriptase, sonic hedgehog, B cell lymphoma murine like site 1, and GATA like transcription factor 1. Additionally, MUC13-overexpressing cells showed increased HER2 and P-ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13 promoter. IL6 treatment of colon cancer cells increased the expression of MUC13 via activation of the JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5 signaling by chemical inhibitors abolished IL6-induced MUC13 expression. IHC analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as compared to adjacent normal tissue.

Conclusions

The results of this study, for the first time, suggest functional roles of MUC13 in colon cancer progression and provide information regarding the regulation of MUC13 expression via JAK2/STAT5 which may reveal promising therapeutic approaches for colon cancer treatment.

Keywords

IL6 MUC13 regulation Transcription factors JAK2/STAT5