Cisplatin resistance in an ovarian cancer model is mediated by the microtubule dynamics regulator TPPP3 which synergizes with tubulin code rewiring

Using RNA-seq, we show that ovarian cancer cells undergo broad changes in the microtubule cytoskeleton that correlate with resistance. Consistent with this, we find that cisplatin directly impacts microtubule dynamics in vitro and in cells.

Paclitaxel counteracts cisplatin and increases resistance. By purifying tubulin from cisplatin sensitive resistant and re-sensitized ovarian cancer cells, we demonstrate that resistance acquisition rewires the tubulin code leading to microtubule stabilization. Furthermore, tubulin polymerization promoting protein 3 (TPPP3) contributes to resistance.