Oncogenic Notch Triggers Neoplastic Tumorigenesis in a Transition-Zone-like Tissue Microenvironment.
During the initial stages of tumorigenesis, the tissue microenvironment where the pro-tumor cells reside plays a crucial role in determining the fate of these cells. Transition zones, where two types of epithelial cells meet, are high-risk sites for carcinogenesis, but the underlying mechanism remains largely unclear. Here, we show that persistent upregulation of Notch signaling induces neoplastic tumorigenesis in a transition zone between the salivary gland imaginal ring cells and the giant cells in Drosophila larvae. In this region, local endogenous JAK-STAT and JNK signaling creates a tissue microenvironment that is susceptible to oncogenic-Notch-induced tumorigenesis, whereas the rest of the salivary gland imaginal ring is refractory to Notch-induced tumor transformation. JNK signaling activates a matrix metalloprotease (MMP1) to promote Notch-induced tumorigenesis at the transition zone. These findings illustrate the significance of local endogenous inflammatory signaling in primary tumor formation.
['Yang|Sheng-An|SA|', 'Portilla|Juan-Martin|JM|', 'Mihailovic|Sonja|S|', 'Huang|Yi-Chun|YC|', 'Deng|Wu-Min|WM|']
D000818:Animals D063646:Carcinogenesis D002471:Cell Transformation, Neoplastic D029721:Drosophila Proteins D004331:Drosophila melanogaster D004847:Epithelial Cells D060227:Imaginal Discs D053612:Janus Kinases D020935:MAP Kinase Signaling System D009369:Neoplasms D051880:Receptors, Notch D012469:Salivary Glands D015398:Signal Transduction D059016:Tumor Microenvironment
Notch tumorigenesis transition zone imaginal rings JAK-STAT JNK MMP tumor hotspot