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Fig. 5 | BMC Cancer

Fig. 5

From: Tyrosine kinase inhibitor SU11274 increased tumorigenicity and enriched for melanoma-initiating cells by bioenergetic modulation

Fig. 5

Bioenergetic modulation counteracts the protumorigenic action of the SU11274. a–b Protein lysates were prepared from untreated controls and Rel3 cells treated with 1 μM SU11274 in spheroid conditions for 7 days. Pluripotent stem cell array has shown expression of all pluripotency markers in Rel3 cells expanded as spheroids. SU11274 treatment further increased level of proteins associated with pluripotency in SU11274-treated cells correlating with their higher tumor initiating properties. Phosphokinase assay screening has shown several active intracellular signaling cascades. Phosphorylated forms of p53 (S392 and S46) were detected in the SU11274-treated cells (lower panel B), which correlates with SU11274 mediated inhibition of cell proliferation. RSK1/2/3 (S380) phosphorylation was increased in SU11274-treated cells. We detected phosphorylation of the following target kinases: ERK1/2 (T202/Y204, T185/Y187), P-RAS40 (T246), Akt 1/2/3 (S473), p38 alpha (T180/Y182), AMPK alpha1 (T183), CREB (S133), GSK-3 alpha/beta(S21/S9), WNK-1 (T60) and HSP60 in both treated and untreated cells

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