Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer.

Zhongbo Zhang, Yuanhong Xu, Chenghai Zhao

Cancer medicine 2021 May

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Mining databases and data obtained from assays on human specimens had shown that Fzd7 is closely associated with Wnt7b, that Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. Fzd7/Wnt7b knockdown in Capan-2 and Panc-1 cells reduced the proliferative capacity of pancreatic cancer stem cells (PCSCs), reduced drug resistance, decreased the percentage of CD24+ CD44+ subset of cells and the levels of ABCG2, inhibited cell-sphere formation, and reduced gemcitabine (GEM) resistance. In contrast, Fzd7/Wnt7b overexpression increased the percentage of the CD24+ CD44+ subset of cells, and increased the levels of ABCG2 detected in cell spheroids. The gem-resistant cells exhibited higher levels of Fzd7/Wnt7b expression, an increased percentage of CD24+ CD44+ cells, and higher levels of ABCG2 compared with the parental cells. Taken together, Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of CSCs. Mechanistically, Fzd7 binds with Wnt7b and modulates the levels of β-catenin, and they may exert their role via modulation of the canonical Wnt pathway. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Citation

Zhongbo Zhang, Yuanhong Xu, Chenghai Zhao. Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer. Cancer medicine. 2021 May;10(10):3332-3345