Developmental fate dictates tumor suppressionin distinct tissuemicroenvironments of Drosophila epithelium

Carcinogenesis is a multi-step process that involves accumulation of mutation within the initiated tumor as well as complex interaction with the surrounding microenvironment. Genetic and developmental basis of tissue microenvironmental regulation of tumor progression, however, is poorly understood. Using the Drosophila genetic mosaic model of tumor development, here I have shown that cells with loss of the Drosophila neoplastic tumor suppressor lethal giant larvae (lgl)display tumorous transformation only in the proximal but not in the distal wing domain. Somatic clones of lgl are normally eliminated from the disc epithelium due to cell competition from the surrounding healthy cells. However, the barrier of cell competition can be breached in the proximal wing domain by additional genetic mis-expression in either the surrounding tissue (Minute genetic background), or by mis-expression of co-operating partners and apoptotic pathway within the tumorous clone (Hippo, Wingless, Decapentaplagic, Notch, Ras signaling, RHG genes). Once the initiated tumor escapes cell competition mediated cell death it is able to manifest into neoplastic tumors in proximal wing domain. The distal wing domain however remains more resistant to tumor progression as the initiated clonescontinue to undergo apoptotic elimination in different genetic backgrounds.Cancer resistance in the distal domain, however, could be breached when host genetic background simultaneously compromised cell death and cell competition. Thus the proximal and distal developmental domains of the wing imaginal disc epithelium act as distinct tissue microenvironments for tumor progression.