LAUSR

Cancer metastasis causes the increase of mortality in most cancer patients, and abnormal cell migration contributes to this disease progression. To control cell migration, the dynamical control of a protein complex within focal adhesions has to be regulated appropriately. It is known that focal adhesions can be regulated dynamically by microtubules. To examine the effects of centrosomal microtubules and non-centrosomal microtubules in regulating focal adhesion dynamics and directed cell migration, we first generated centrosome-deficient cells. We find that centrosomal microtubules and non-centrosomal microtubules control focal adhesion dynamics through modulating focal adhesion composition, which dynamically control the activity of small GTPases Rac1 and Cdc42. Deficiency of centrosomal microtubules significantly disrupts the balance of Rac1 and Cdc42, thereby inhibiting directed cell migration. This study reveals the effects of centrosome in focal adhesions, and indicates an important role for Rac1 and Cdc42 activation that controls actin polymerization, cell polarization and directed cell migration. Citation Format: Jean-Cheng Kuo. Coordination of Rac1 and Cdc42 by centrosomal microtubules in focal adhesion dynamics and directed cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1877. doi:10.1158/1538-7445.AM2017-1877