Functions and regulation of MUC13 mucin in colon cancer cells

Brij K. Gupta, Diane M. Maher, Mara C. Ebeling, Phillip D. Stephenson, Susan E. Puumala, Michael R. Koch, Hiroyuki Aburatani, Meena Jaggi, Subhash Chauhan

Research output: Contribution to journalArticle

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Abstract

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.

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

Original languageEnglish (US)
Pages (from-to)1378-1391
Number of pages14
JournalJournal of Gastroenterology
Volume49
Issue number10
DOIs
StatePublished - Oct 7 2014

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Mucins
Colonic Neoplasms
Interleukin-6
Chromatin Immunoprecipitation
Cell Movement
Immunohistochemistry
GATA Transcription Factors
Telomerase
B-Cell Lymphoma
Therapeutics
Growth
Proteins
Cell Line
Neoplasms

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Gupta, B. K., Maher, D. M., Ebeling, M. C., Stephenson, P. D., Puumala, S. E., Koch, M. R., ... Chauhan, S. (2014). Functions and regulation of MUC13 mucin in colon cancer cells. Journal of Gastroenterology, 49(10), 1378-1391. https://doi.org/10.1007/s00535-013-0885-z

Functions and regulation of MUC13 mucin in colon cancer cells. / Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Stephenson, Phillip D.; Puumala, Susan E.; Koch, Michael R.; Aburatani, Hiroyuki; Jaggi, Meena; Chauhan, Subhash.

In: Journal of Gastroenterology, Vol. 49, No. 10, 07.10.2014, p. 1378-1391.

Research output: Contribution to journalArticle

Gupta, BK, Maher, DM, Ebeling, MC, Stephenson, PD, Puumala, SE, Koch, MR, Aburatani, H, Jaggi, M & Chauhan, S 2014, 'Functions and regulation of MUC13 mucin in colon cancer cells', Journal of Gastroenterology, vol. 49, no. 10, pp. 1378-1391. https://doi.org/10.1007/s00535-013-0885-z
Gupta BK, Maher DM, Ebeling MC, Stephenson PD, Puumala SE, Koch MR et al. Functions and regulation of MUC13 mucin in colon cancer cells. Journal of Gastroenterology. 2014 Oct 7;49(10):1378-1391. https://doi.org/10.1007/s00535-013-0885-z
Gupta, Brij K. ; Maher, Diane M. ; Ebeling, Mara C. ; Stephenson, Phillip D. ; Puumala, Susan E. ; Koch, Michael R. ; Aburatani, Hiroyuki ; Jaggi, Meena ; Chauhan, Subhash. / Functions and regulation of MUC13 mucin in colon cancer cells. In: Journal of Gastroenterology. 2014 ; Vol. 49, No. 10. pp. 1378-1391.
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AU - Gupta, Brij K.

AU - Maher, Diane M.

AU - Ebeling, Mara C.

AU - Stephenson, Phillip D.

AU - Puumala, Susan E.

AU - Koch, Michael R.

AU - Aburatani, Hiroyuki

AU - Jaggi, Meena

AU - Chauhan, Subhash

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N2 - 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.Background: MUC13 is overexpressed and aberrantly localized in colon cancer tissue; however, the specific functions and regulation of MUC13 expression are unknown.

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

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