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Fig. 4 | Molecular Cancer

Fig. 4

From: Correction to: Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma

Fig. 4

SNS-032 impairs properties of cancer stem-like cells through lowering transcription factor KLF4 in UM cells. a SNS-032 suppressed melanosphere growth and serially replating capacity in UM cells. Twenty-four hours after treatment with SNS-032 (0.25 μM), Mel270 and Omm2.3 cells were harvested, suspended in stem cell culture medium, and plated in ultra-low attachment 24-well plates (1000 cells/well). Melanospheres were counted on day 7. The cells were then harvested and performed for the secondary and tertiary rounds of melanosphere culture, respectively. *, P < 0.05; **, P < 0.01; ***, P < 0.001, Student’s t test. b SNS-032 decreased ALDH+ cells in UM cells. Mel270 and Omm2.3 cells were treated with SNS-032 for 48 h, the percentage of ALDH+ cells was detected by flow cytometry. Quantitive analysis of ALDH+ cells from three independent experiments is shown. ***, P < 0.001, Student’s t test. c SNS-032 reduced the frequency of CSCs in UM performed by limiting dilution assay in NOD-SCID mice. Representative images of tumor removed from the mice of each group are shown (left). The frequency of CSCs in UM is shown (right). d SNS-032 decreased the protein levels of KLF4. UM cells were exposed to SNS-032 for 48 h, the levels of stemness-related proteins were detected by Western blot analysis. e SNS-032 inhibited the gene transcription of KLF4. The mRNA levels of KLF4 were measured after 24 h exposure to SNS-032 by qRT-PCR, and expressed as relative levels compared with controls. *, P < 0.05; **, P < 0.01; ***, P < 0.0001, one-way ANOVA, post hoc intergroup comparisons, Tukey’s test. fh Ectopic expression of KLF4 attenuated SNS-032-mediated decrease of CSCs properties in UM cells. f The protein levels of KLF4 were examined by Western blot analysis after Mel270 cells stably transduced with lentiviral vector or construct encoding human KLF4. g Ectopic expression of KLF4 increases self-renewal capacity evaluated by melanosphere growth and serially replating assay. h Overexpression of KLF4 increases the percentage of ALDH+ cells detected by flow cytometry. i-k Silencing KLF4 potentiated SNS-032-mediated decrease of CSCs properties in UM cells. i The protein levels of KLF4 were examined by Western blot analysis after Mel270 cells stably transduced with lentiviral vector or shRNAs against human KLF4. j Knockdown of KLF4 decreased melanosphere growth and serially replating capacity. k Knockdown of KLF4 reduced the percentage of ALDH+ cells. *, P < 0.05; **, P < 0.01; ***, P < 0.001, Student’s t test

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