DOAJ Open Access 2021

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

Dipsikha Biswas Logan Slade Luke Duffley Neil Mueller Khoi Thien Dao +5 lainnya

Abstrak

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.

Penulis (10)

D

Dipsikha Biswas

L

Logan Slade

L

Luke Duffley

N

Neil Mueller

K

Khoi Thien Dao

A

Angella Mercer

S

Shanmugasundaram Pakkiriswami

Y

Yassine El Hiani

P

Petra C. Kienesberger

T

Thomas Pulinilkunnil

Format Sitasi

Biswas, D., Slade, L., Duffley, L., Mueller, N., Dao, K.T., Mercer, A. et al. (2021). Inhibiting BCKDK in triple negative breast cancer suppresses protein translation, impairs mitochondrial function, and potentiates doxorubicin cytotoxicity. https://doi.org/10.1038/s41420-021-00602-0

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Informasi Jurnal
Tahun Terbit
2021
Sumber Database
DOAJ
DOI
10.1038/s41420-021-00602-0
Akses
Open Access ✓