Department of Pancreatic and Biliary Surgery, The First Hospital of China Medical University, Shenyang, P.R. China.
Department of Pathophysiology, Basic Medical College, China Medical University, Shenyang, P.R. China.
Cancer Med. 2021 May;10(10):3332-3345. doi: 10.1002/cam4.3819. Epub 2021 May 2.
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.
从人类标本的检测中挖掘数据库和数据表明，Fzd7 与 Wnt7b 密切相关，与正常组织相比，Fzd7/Wnt7b 在胰腺癌组织中的表达上调，其表达与存活率呈负相关。在 Capan-2 和 Panc-1 细胞中敲低 Fzd7/Wnt7b 降低了胰腺癌干细胞（PCSCs）的增殖能力，降低了耐药性，降低了 CD24 CD44 亚群细胞的比例和 ABCG2 的水平，抑制了细胞球的形成，并降低了吉西他滨（GEM）的耐药性。相比之下，Fzd7/Wnt7b 的过表达增加了 CD24 CD44 亚群细胞的比例，并增加了细胞球体中检测到的 ABCG2 水平。与亲本细胞相比，耐药细胞表现出更高水平的 Fzd7/Wnt7b 表达、更高比例的 CD24 CD44 细胞和更高水平的 ABCG2。总之，Fzd7/Wnt7b 的敲低可以通过降低 CSCs 的比例来降低 PDAC 细胞的干性和化疗耐药性。从机制上讲，Fzd7 与 Wnt7b 结合并调节 β-连环蛋白的水平，它们可能通过调节经典 Wnt 通路发挥作用。
