Effect of MUC1/β-catenin interaction on the tumorigenic capacity of pancreatic CD133+ cells
Year: 2016
Type: article
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 accordingly 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.
Source: Oncology Letters
DOI: 10.3892/ol.2016.4888
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2499477582