Ribosomal Protein S6 Kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein

Table 1 Effect of Various Small Chemical Inhibitors on MSP-Induced Spindle-Like Morphologies in RON-Expressing MDCK cells*

Small molecule inhibitors	Signal proteins inhibited	Amount used to treat cells	Cell elongation index	Preventive effect (%)
Control	N/A	N/A	1.0 ± 0.24	None
MSP	none	2.0 nM	3.12 ± 0.47	N.D
CP-1	RON	100 μM	1.05 ± 0.26	98.4%
PD98059	MEK1/2	100 μM	1.03 ± 0.31	97.1%
Wortmannin	PI-3 kinase	50 μM	2.9 ± 0.41	7.1%
SB203580	p38 MAP kinase	50 μM	3.1 ± 4.6	0.6%
SP600125	JNK1,2,3	5 μM	3.07 ± 0.39	1.6%
Cay10512	NF-κB	5 μM	2.03 ± 0.33	39.4%
S31-201	Stat3	10 μM	1.25 ± 0.34	59.9%
XAV-939	Wnt/β-catenin	5 μM	2.16 ± 0.32	30.8%
SL0101	RSK	50 μM	1.09 ± 0.27	97.1%
Rapamycin	FRAP/mTOR	100 nM	2.69 ± 0.25	13.8%
Vismodegib	Hedgehog	1 μM	2.04 ± 0.22	34.6%
SB431542	TGF-β1 receptor	1 μM	2.97 ± 0.24	4.8%

*M-RON cells (1 × 10⁴ cells/well) in DMEM containing 1% FBS were stimulated with 2 nM of MSP in the presence of absence of individual small chemical inhibitors for 24 h. Cell morphological changes were observed under microscope and photographed with CCD camera. Cell elongation index (CEI) was determined by measuring the length of individual adherent cells among various groups. CEI from control cells was set as one. The percentages of preventive effect were calculated by comparing with as the CEI from MSP-treated cells previously described [45]