Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and
tumor samples derived from ALK-positive
anaplastic large cell lymphoma (ALK(+)ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK(+)ALCL can be attributed to
nucleophosmin-anaplastic lymphoma kinase (
NPM-ALK), the oncogenic fusion
protein carrying a central pathogenetic role in these
tumors. By confocal microscopy, Sox2
protein was detectable in virtually all cells in ALK(+)ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using
short interfering RNA in isolated Sox2(active) cells, but not Sox2(inactive) cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK(+)ALCL represents the first example of a
hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which
NPM-ALK mediates
tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in
cancer cells.