STAT3 and ERK1/2 Cross-talk in Leukaemia Inhibitory Factor Mediated Trophoblastic JEG-3 Cell Invasion and Expression of Mucin 1 and Fos

Abstract

PROBLEM:

The aim of this study was to investigate the relative importance of STAT3 and ERK1/2 activation in leukaemia inhibitory factor (LIF)-mediated invasion of JEG-3 cells. METHOD OF STUDY:

Matrigel matrix-based invasion assay; Western blot; cDNA microarray; quantitative RT-PCR; gene silencing by siRNA. RESULTS:

Leukaemia inhibitory factor treatment led to the activation of STAT3 and ERK1/2 signaling pathways which was followed by changes in the expression of several invasion-associated molecules such as mucin1 (MUC1), Fos, Jun, etc. Abrogation of either STAT3 or ERK1/2 signaling reduced (P < 0.05) the LIF-mediated invasion of JEG-3 cells. It was associated with a significant reduction in the expression of both MUC1 and Fos, suggesting a common denominator in LIF-STAT3-ERK1/2 signaling. To this effect, we observed a decrease in LIF-mediated p-STAT3 (Ser727) upon blocking STAT3 or ERK1/2 signaling. CONCLUSIONS:

ERK1/2 as well as JAK-STAT-mediated STAT3 (Ser727) phosphorylation play an important role in LIF-mediated JEG-3 trophoblastic cell invasion and gene expression.