Oct4 is mainly expressed in embryonic stem cells(ESCs),germline stem cells,and embryonal carcinoma cells(ECCs)and plays an indispensable role in maintaining the pluripotency and self-renewal of these pluripotent stem cells.Akt serine/threonine kinase,a wellestablished anti-apoptosis and cell survival factor,has also been implicated as an important regulator of stemness.Emerging evidence indicated that Oct4 is reciprocally connected to Akt via a number of routes,and moreover,a direct interaction between Oct4 and Akt has recently been revealed.These components collectively form the Akt–Oct4 regulatory circuit.In this review,we summarize our current knowledge about the Akt–Oct4 regulatory circuit in ESCs and discuss its alterations in ECCs that may underlie the tumorigenesis of pluripotent stem cells. Oct4 is mainly expressed in embryonic stem cells (ESCs), germline stem cells, and embryonal carcinoma cells (ECCs) and plays an indispensable role in maintaining the pluripotency and self-renewal of these pluripotent stem cells. Akt serine / threonine kinase, a wellestablished anti-apoptosis and cell survival factor, has also been implicated as an important regulator of stemness. Emerging evidence that Oct4 is reciprocally connected to Akt via a number of routes, and moreover, a direct interaction between Oct4 and Akt has recently been revealed. These components collectively form the Akt-Oct4 regulatory circuit. In this review, we summarize our current knowledge about the Akt-Oct4 regulatory circuit in ESCs and discuss its alterations in ECCs that may underlie the tumorigenesis of pluripotent stem cells.