Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Figure 1

LIF signaling maintains ECCs pluripotency. In pluripotent ECC lines, LIF binds to the LIF receptor (LIFR) and gp130 recruiting Janus Kinase (JAK), which in turn phosphorylates and activates Signal Transducer and Activator of Transcription 3 (STAT3). Phosphorylated STAT3 homodimerizes and translocates to the nucleus promoting the expression of pluripotency genes encoding OCT4, SOX2, and NANOG. During differentiation, LIF levels decline substantially leading to decreased phosphorylated STAT3, which is augmented by the tyrosine-specific protein phosphatase SHP-1. The decline in active STAT3 reduces the expression of pluripotency genes.