Fig. 6: KIFC1-S26 phosphorylation induces drug resistance.

a, c–f KIFC1-S26 phosphorylation induces etoposide resistance. b, g–j Etoposide-resistance is restrained by ATM/ATR inhibitor VE-822. a, b The indicated stable cell lines were treated with etoposide (0.5 μM) or VE-822 (5 μM) for 4 days, and then were analyzed for cell viability using the MTT assay. Histogram graphs showing the percentage of surviving cells. a Two-tailed t test p values (from left to right): p = 0.0007, 0.0099, and 0.0090. b Two-tailed t test p values (from left to right): p = 0.0005, 0.0110, and 0.0143. c, g Xenograft experiment with KIFC1-WT, S26A, or S26D stable cells was described in the Methods section. Tumors were collected and photographed (scale bar, 2 cm). d, e, h, i Quantification of average tumor volume (d, h) and weight (e, i). Six tumors were included in each group. d Two-tailed t test p values (from left to right): p = 0.0062 and 0.00001. (e) Two-tailed t test p values: p = 0.0099 and 0.00001. h Two-tailed t test p values: p = 0.0053 and 0.0016. i Two-tailed t test p values: p = 0.0057 and 0.0016. f, j Representative immunohistochemical images showing γ-tubulin staining (scale bar, 10 μm) with quantitative analysis of pseudo-bipolar (centrosome clustering) and multipolar mitosis of the tumor sections of xenograft tumor samples after treatment with etoposide or VE-822. Arrows point to the centrosomes. For each experimental condition, 100–161 cells were counted, and three independent experiments were performed. f Two-tailed t test p values: p = 0.0016, 0.9245, and 0.5663. j Two-tailed t test p values: p = 0.0006 and 0.0092. Data represent the mean ± SD of three times of independent experiments. NS = not significant, *p < 0.05, **p < 0.01, Source data are provided as a Source Data file.