Wnt 通路的激活是许多人类癌症的核心。 Wnt 和巨胞饮作用通常在同一过程中活跃，了解 Wnt 信号传导和膜运输如何合作应该可以提高我们对胚胎发育和癌症的理解。在这里，我们发现巨胞饮激活剂，即肿瘤启动子佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA)，可以增强 Wnt 信号传导。使用非洲爪蟾胚胎作为体内模型的实验表明，PMA 佛波酯和 Wnt 信号传导之间存在显着的协同作用，而 Wnt 信号传导被巨胞饮作用、Rac1 活性和溶酶体酸化抑制剂所阻断。人类结直肠癌组织阵列和小鼠异种移植物显示癌症进展与巨胞饮/多泡体/溶酶体标记物增加和 GSK3 水平降低相关。经典 Wnt、粘着斑、溶酶体和巨胞饮作用之间的串扰表明了 Wnt 驱动的癌症进展的可能治疗靶标。© 2023，Tejeda-Munoz、Azbazdar 等人。

Activation of the Wnt pathway lies at the core of many human cancers. Wnt and macropinocytosis are often active in the same processes, and understanding how Wnt signaling and membrane trafficking cooperate should improve our understanding of embryonic development and cancer. Here, we show that a macropinocytosis activator, the tumor promoter phorbol 12-myristate 13-acetate (PMA), enhances Wnt signaling. Experiments using the Xenopus embryo as an in vivo model showed marked cooperation between the PMA phorbol ester and Wnt signaling, which was blocked by inhibitors of macropinocytosis, Rac1 activity, and lysosome acidification. Human colorectal cancer tissue arrays and xenografts in mice showed a correlation of cancer progression with increased macropinocytosis/multivesicular body/lysosome markers and decreased GSK3 levels. The crosstalk between canonical Wnt, focal adhesions, lysosomes, and macropinocytosis suggests possible therapeutic targets for cancer progression in Wnt-driven cancers.© 2023, Tejeda-Munoz, Azbazdar et al.