The role of Yamanaka cocktail transcription factors (OCT4, SOX2, KLF4, c-Myc) in the differentiation of somatic cells, their malignant transformation, and tumor progression

Abstract

The paper reviews the role of transcription factors that are part of the Yamanaka cocktail (OCT4, SOX2, KLF4, and c-Myc) in the mechanisms of tumor stem cell (TSC) differentiation (a pool of pluripotent cells), their participation in the malignant transformation of somatic cells, and in tumor progression. Their increased proliferative activity, which determines their malignant potential, was believed to be the main feature of tumor cells. Currently, there is more evidence supporting another concept that explains the continued tumor growth, metastasis, and resistance to therapy of most malignant tumors with a small, rest-ing, and rarely dividing population of pluripotent tumor cells. Year 2006 is considered to be the beginning of a new direction in developmental biology when Japanese researchers K. Takahashi and S. Yamanaka published the results of their studies on the properties of embryonic stem cells and experiments on direct reprogramming of somatic terminally differentiated cells.The research proved that four transcription factors were sufficient to maintain the pluripotent properties of cells, namely Oct4, SOX2, KLF4, and c-Myc, which were later called the Yamanaka cocktail. Such factors as SOX2and Oct4 are at the top of the hierarchy of transcription factors that regulate the pluripotent proper-ties of cells, their differentiation, and dedifferentiation. TSCs represent, albeit a complex, but very promising target for the development of innovative products for the diagnosis of and targeted therapy for neoplasms. From this point of view, the factors of pluripotency, which are parts of the Yamanaka cocktail, could be such promising targets, whose effect will probably be able to suppress or reduce the malignant potential of the most aggressive tumors and even prevent carcinogenic transformation in cases of precancerous pathology. Keywords: Yamanaka cocktail, OCT4, SOX2, KLF4, c-Myc, malignant transformation