Effect of MUC1/beta-catenin interaction on the tumorigenic capacity of pancreatic CD133(+) cells

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Sousa, AM (Author) Other; Rei, M (Author) Other; Freitas, R (Author) Other; Ricardo, S (Author) Other; Caffrey, T (Author) Other; David L (Author) FMUP; Raquel Almeida (Author) FCUP; Hollingsworth, MA (Author) Other; Santos-Silva F (Author) FMUP

Journal

Title: Oncology Letters

Vol. 12

Pages: 1811-1817

ISSN: 1792-1074

Publisher: Spandidos Publications

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Other information

Authenticus ID: P-00K-NYJ

DOI: 10.3892/ol.2016.4888

Abstract (EN): 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 beta-catenin, were characterized in HPAF-II CD133(+) and CD133(low) cell subpopulations and in tumor xenografts generated from these cells. Compared with HPAF CD133(low) cells, HPAF-II CD133(+) cancer cells exhibited increased tumorigenic potential in immunocompromised mice, which was associated with overexpression of MUC1 and with the accordingly altered expression profile of MUC1-associated signaling partners. Additionally, MUC1-CD/beta-catenin interactions were increased both in the HPAF-II CD133(+) cell subpopulation and derived tumor xenografts compared with HPAF CD133(low) cells. These results suggest that, in comparison with HPAF CD133(low) cells, CD133(+) cells exhibit higher expression of MUC1, which contributes to their tumorigenic phenotype through increased interaction between MUC1-CD and beta-catenin, which in turn modulates oncogenic signaling cascades.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7