Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through dysregulation of the mitochondrial permeability transition pore.

ABSTRACT: Cdk5, which plays a role in the development and progression of many human cancers, localizes in the mitochondria, a key determinant of apoptotic cell death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss increases chemotherapy-induced apoptosis. However, the molecular mechanism by which Cdk5 loss promotes cell death remains unclear. Here, we investigate the possibility that Cdk5 loss activates the intrinsic apoptotic pathway in breast cancer cells. We demonstrate that Cdk5-deficient breast cancer cells exhibit increased mitochondrial depolarization, mitochondrial ROS levels, and mitochondrial fragmentation that is associated with an increase in both intracellular Ca²⁺ level and calcineurin activity, and DRP1 S637 dephosphorylation. These events accomp

SUBMITTER: NavaneethaKrishnan S 

PROVIDER: S-EPMC5874258 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature