An increasing body of evidence suggests that tumors may originate from a few transformed cells with stem-cell characteristics, called cancer stem cells.This hypothesis is based on observations that some solid tumors and leukaemias contain small numbers of self-renewing cells that can recreate the whole tumor mass when transplanted in mice.However, it remains unclear how normal stem cells are transformed into cancer stem cells.My laboratory identified multipotent renal and nephric stem cells (RNSCs) in the adult Drosophila kidney (Malpighian Tubules or MTs).In a recent genetic screen for mutants that affect RNSC self-renewal and differentiation, we identified that activation of the oncogene Ras caused RNSC overproliferation and resulted in tumorous growth.In wild type MTs, each stem cell generates one self-renewing and one differentiating daughter cells; in stem ceils expressing a constitutively activated form of Ras, both daughter cells grow and behave like stem cells leading to the formation of tumors in MTs.The Ras transformed stem cells exhibited all hallmarks of cancer, such as increasing proliferation, overiding cell death, failure to differentiate, and enhanced migration through up-regulating Cyclin E, dMyc, DIAP, MMP1, and several other genes.We further demonstrated that several signal transdution pathways cooperatively mediate Ras-function in the stem cell transformation.Therefore, we have identified a molecular mechanism that regulates stem cell transformation and maybe useful to prevent tumor formation in certain organs.