Reorganization of paclitaxel-stabilized microtubule arrays at mitotic entry: roles of depolymerizing kinesins and severing proteins.

Reorganization of paclitaxel-stabilized microtubule arrays at mitotic entry: roles of depolymerizing kinesins and severing proteins. Cancer Biol Ther. 2019 Jul 25;:1-11 Authors: Leung JC, Cassimeris L Abstract Paclitaxel is a widely used anti-cancer treatment that disrupts cell cycle progression by blocking cells in mitosis. The block at mitosis, with spindles assembled from short microtubules, is surprising given paclitaxel's microtubule stabilizing activity and the need to depolymerize long interphase microtubules prior to spindle formation. Cells must antagonize paclitaxel's microtubule stabilizing activity during a brief window of time at the transition from interphase to mitosis, allowing microtubule reorganization into a mitotic spindle, although the mechanism underlying microtubule depolymerization in the presence of paclitaxel has not been examined. Here we test the hypothesis that microtubule severing and/or depolymerizing proteins active at mitotic entry are necessary to clear the interphase array in paclitaxel-treated cells and allow subsequent formation of mitotic spindles formed of short microtubules. A549 and LLC-PK1 cells treated with 30nM paclitaxel approximately 4 h prior to mitotic entry successfully progress through the G2/M transition by clearing the interphase microtubule array from the cell interior outward to the cell periphery, a spatial pattern of reorganization that differs from that of cells possessing dyn...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research