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The analysis of conditions and possible mechanisms of activation of 96 genes providing a malignant/pluripotent phenotype of Krebs-2 cancer stem cells have been performed. Three stress factors combined into the single concept of "generalized cellular stress", which are supposed to regulate the expression of these genes, are determined. Additionally, for these genes, the presence of binding sites for transcription factors that are being activated in response to factors of generalized cellular stress has been established. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem-like phenotype of tumor cells under conditions of generalized cellular stress.

Functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. Genes were assigned to the three functional groups that determine the malignant phenotype of cancer cells. These groups represent the following features of tumor cells: proliferative self-sufficiency, invasive growth and metastasis, and multiple drug resistance. Malignancy of cancer stem cells was found to be provided by the same genes that provide the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is just the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches.