STAT3 and ERK1/2 cross-talk in leukaemia inhibitory factor mediated trophoblastic JEG-3 cell invasion and expression of mucin 1 and Fos.
OBJECTIVE
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.


METHODS
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.
Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
Pankaj
P
Suman
Satish Kumar
SK
Gupta
D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*
C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D018396:Mucin-1; D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
ERK1/2; JEG-3; Leukaemia inhibitory factor; STAT3; microarray; trophoblast invasion