Fig. 3
From: Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia
Acquisition of TKI resistance via FLT3-JAK-STAT3-TAZ and Hippo-TAZ signaling in BP-CML. A Immunoblotting analysis of FLT3, BCR::ABL1, and their downstream signaling components in spontaneous imatinib-resistant K562 cells (IM-0.4R, 0.4 μM imatinib-resistant cells; IM-1R, 1 μM imatinib-resistant cells) compared to FLT3-mediated TKI-resistant K562-FLT3-IR, -NR, and -DR cells. B and C Representative immunofluorescence images of the nuclear localization of TAZ (green) and p-STAT3 (green) in K562-FLT3-IR cells. D Immunoblotting analysis of FLT3-pSTAT3-TAZ signaling components in K562-FLT3-IR cells treated for 16 h with increasing doses of quizartinib (QZ; 0, 3, 10, 30, 100 nM). E Measurements of TAZ transcript levels in K562-FLT3-IR cells treated for 16 h with 30 nM quizartinib. ****p < 0.0001. F Immunoblotting analysis of FLT3-pSTAT3-TAZ signaling components in K562-FLT3-IR and K562-TAZ cells treated with various doses of midostaurin (MD; 0, 0.1, 0.3 μM) for 16 h. G Immunoblotting analysis of FLT3-pSTAT3-TAZ signaling components in K562-FLT3-IR cells treated with various doses of JAK inhibitor AZD-1480 treatment (AZD; 0, 0.1, 0.3, 1, 3 μM) for 16 h. ***p < 0.001. H Measurements of TAZ transcript levels in K562-FLT3-IR cells treated for 16 h with 2.5 μM AZD-1480. I Immunoblotting analysis of FLT3-pSTAT3-TAZ signaling components in K562-FLT3-IR cells treated with various doses of BP-1–102 (0, 1, 5, 10 μM) for 16 h. J Immunoblotting analysis of FLT3-pSTAT3-TAZ signaling components in MDA-MD-231 breast cancer cells after treatments with 30 nM quizartinib (QZ), 0.3 μM midostaurin (MD), 3 μM AZD-1480 (AZD), and 30 μM C188-9. K Immunoblotting analysis of TAZ protein in control or LATS1/2-depleted K562-FLT3-IR cells treated with the Hippo pathway activators 2-DG (6.25 mM) or LatB (1 μg/ml) for 16 h. s.e, short exposure. L Schematic illustrating the transcriptional and post-translational mechanisms that regulate TAZ in BP-CML. E, H All p-values were calculated using Student’s t-tests and error bars are means of triplicates ± SD. A p-value of less than 0.05 indicates a statistical difference