Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity

Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity

Proposed mechanism. A Doxorubicin (DOX) targets the BCAA catabolic pathway in TNBCs, by downregulating BCKDK and augmenting clearance of intracellular BCKAs. B Genetic or pharmacological (high BT2 concentration) inhibition of BCKDK results in increased cell death, decreased intracellular BCKAs, dysr...

Full description

Bibliographic Details
Main Authors: Dipsikha Biswas, Logan Slade, Luke Duffley, Neil Mueller, Khoi Thien Dao, Angella Mercer, Shanmugasundaram Pakkiriswami, Yassine El Hiani, Petra C. Kienesberger, Thomas Pulinilkunnil
Format: Article
Language:English
Published: Nature Publishing Group 2021-09-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-021-00602-0
Description
Summary:Proposed mechanism. A Doxorubicin (DOX) targets the BCAA catabolic pathway in TNBCs, by downregulating BCKDK and augmenting clearance of intracellular BCKAs. B Genetic or pharmacological (high BT2 concentration) inhibition of BCKDK results in increased cell death, decreased intracellular BCKAs, dysregulated mitochondrial function, ATP insufficiency, SESN2 activation, and inhibition of mTORC1 signaling and protein synthesis. C BCKDK inhibition (siRNA mediated or low-BT2 concentration) exacerbates DOX-induced cytotoxicity and caspase activity.
ISSN:2058-7716

Similar Items