Effect of MUC1/β-catenin interaction on the tumorigenic capacity of pancreatic CD133+ cells

Andreia Mota Sousa, Margarida Rei, Rita Freitas, Sara Ricardo, Thomas Caffrey, Leonor David, Raquel Almeida, Michael A Hollingsworth, Filipe Santos-Silva

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2 Scopus citations

Abstract

Despite the fact that the biological function of cluster of differentiation (CD)133 remains unclear, this glycoprotein is currently used in the identification and isolation of tumor-initiating cells from certain malignant tumors, including pancreatic cancer. In the present study, the involvement of mucin 1 (MUC1) in the signaling pathways of a highly tumorigenic CD133+ cellular subpopulation sorted from the pancreatic cancer cell line HPAF-II was evaluated. The expression of MUC1-cytoplasmic domain (MUC1-CD) and oncogenic signaling transducers (epidermal growth factor receptor, protein kinase C delta, glycogen synthase kinase 3 beta and growth factor receptor-bound protein 2), as well as the association between MUC1 and β-catenin, were characterized in HPAF-II CD133+ and CD133low cell subpopulations and in tumor xenografts generated from these cells. Compared with HPAF CD133low cells, HPAF-II CD133+ cancer cells exhibited increased tumorigenic potential in immunocompromised mice, which was associated with overexpression of MUC1 and with the accord- ingly altered expression profile of MUC1-associated signaling partners. Additionally, MUC1-CD/β-catenin interactions were increased both in the HPAF-II CD133+ cell subpopulation and derived tumor xenografts compared with HPAF CD133low cells. These results suggest that, in comparison with HPAF CD133low cells, CD133+ cells exhibit higher expression of MUC1, which contributes to their tumorigenic phenotype through increased interaction between MUC1-CD and β-catenin, which in turn modulates oncogenic signaling cascades.

Original languageEnglish (US)
Pages (from-to)1811-1817
Number of pages7
JournalOncology Letters
Volume12
Issue number3
DOIs
Publication statusPublished - Sep 2016

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Keywords

  • Cancer stem cells
  • Cell signaling
  • MUC1
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sousa, A. M., Rei, M., Freitas, R., Ricardo, S., Caffrey, T., David, L., ... Santos-Silva, F. (2016). Effect of MUC1/β-catenin interaction on the tumorigenic capacity of pancreatic CD133+ cells. Oncology Letters, 12(3), 1811-1817. https://doi.org/10.3892/ol.2016.4888