Abstract 5717: CDK4 inhibition suppresses Rab11 mediated collective cell migration in colon cancer cells

Abstract

Abstract In tumor progression, cell proliferation and cell adhesion are critical for tumor growth and metastasis. It has been demonstrated cell division which associated with microtubule organization also has impact on tubulin mediated focal adhesion turnover, however, the mechanism is not clear in the cell cohort migration which is accompanied with both cell proliferation and cell migration. This study is to investigate the effect of cell cycle inhibition in the collective cell migration. HT-29 colon cancer cells were treated with CDK4 inhibitor CINK4, paclitaxel and focal adhesion inhibitor PF573228. The cell proliferation rate was determined by MTT assay, cell migration ability was analyzed by wound healing assay. Rab11, E-cadherin and focal adhesion kinase were revealed by immuno-confocal microscopy. When HT-29 cells were treated with lower dose of CDK4 inhibitor CINK4, cell migration was suppressed. Meanwhile, in the result of immunostaining, the recycling endosomal protein Rab11which is involved in E-cadherin turnover in collective cell migration was not distributed in the cell membrane after CINK4 treatment. Furthermore, when cellular FAK activity were inhibited by PF573228 and tubulin disassembly was inhibited by paclitaxel, the cell area was increased with stable attachment, however, the membrane translocation of Rab11 was not affected. This study demonstrated cell cycle inhibition in G1 phase affected Rab11 mediated collective cell migration through tubulin regulated focal adhesion turnover for cell attachment. Keywords: CDK4, cell cycle, focal adhesion kinase, paclitaxel, colon cancer Citation Format: Chun Pu Cheng, Chia-En Ku, Shin-Ru Lee, Yu-Chun Wang, Yu-Chien Ching, Hui-Chun Chen, Wei-Ting Chao. CDK4 inhibition suppresses Rab11 mediated collective cell migration in colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5717.