细胞生物学
信号转导
河马信号通路
细胞周期蛋白依赖激酶8
癌变
转录因子
基因
表型
细胞信号
GTPase激活蛋白
细胞命运测定
作者
Masato Enomoto,Daisaku Takemoto,Tatsushi Igaki
标识
DOI:10.1016/j.devcel.2021.07.002
摘要
Cancer tissue often comprises multiple tumor clones with distinct oncogenic alterations such as Ras or Src activation, yet the mechanism by which tumor heterogeneity drives cancer progression remains elusive. Here, we show in Drosophila imaginal epithelium that clones of Ras- or Src-activated benign tumors interact with each other to mutually promote tumor malignancy. Mechanistically, Ras-activated cells upregulate the cell-surface ligand Delta while Src-activated cells upregulate its receptor Notch, leading to Notch activation in Src cells. Elevated Notch signaling induces the transcriptional repressor Zfh1/ZEB1, which downregulates E-cadherin and cell death gene hid, leading to Src-activated invasive tumors. Simultaneously, Notch activation in Src cells upregulates the cytokine Unpaired/IL-6, which activates JAK-STAT signaling in neighboring Ras cells. Elevated JAK-STAT signaling upregulates the BTB-zinc-finger protein Chinmo, which downregulates E-cadherin and thus generates Ras-activated invasive tumors. Our findings provide a mechanistic explanation for how tumor heterogeneity triggers tumor progression via cell-cell interactions.
科研通智能强力驱动
Strongly Powered by AbleSci AI