Mechanisms of tumor-cells-invasion in Drosophila wing imaginal disc epithelia

Malignant cancers emerge in epithelial tissues through a progressive process in which a single transformed mutant cell becomes tumorigenic and invasive. Although numerous genes involved in the malignant transformation of cancer cells have been described, how tumor cells launch an invasion into the basal side of epithelial tissues remains elusive. We found, using a Drosophila wing imaginal disc epithelia, that genetically mosaic clones of cells mutant for a neoplastic-tumor-suppressor gene (nTSG) in combination with the oncogenic Ras (RasV12) expression initiate invasion into the basal side of the epithelial layer at specific spots in the epithelial tissue. In this "invasion hotspot" the oncogenic double-mutant cells extruded from the basal side show an endoreplication-dependent polyploidization and invasive phenotypes. Conversely, in other regions of the epithelial tissue, the double-mutant cells deviate from the apical side of the epithelial layer, undergo mitotic cell division, and show a benign tumor growth in the lumen. These data indicate that the onset of tumor-cell invasion is highly dependent on the tissue-intrinsic local microenvironment. To investigate the molecular mechanisms underlying the malignant phenotypes including polyploidization and invasion observed in the oncogenic double-mutant cells, we will determine what types of genes and genetic signaling pathways are related to these processes by single-cell RNA-seq-based transcriptome analysis.