Brain type of creatine kinase induces doxorubicin resistance via TGF-β signaling in MDA-MB-231 breast cancer cells.

Content Provider	Europe PMC
Author	Son, Seogho Yoo, Seung-ah Nam, KeeSoo Oh, Sunhwa Lee, Kyung-min Yi, Jae Youn Shin, Incheol
Copyright Year	2022
Abstract	ABSTRACTBrain type of creatine kinase (CKB) regulates energy homeostasis by reversibly transferring phosphate groups between phosphocreatine and ATP at sites of high energy demand. Several types of cancer cells exhibit upregulated CKB expression, but the function of CKB in cancer cells remains unclear. In this study, we investigated the function of CKB in breast cancer by overexpressing CKB in MDA-MB-231 cells. The overexpression of CKB did not affect cell growth rate, cell cycle distribution, ATP level or key mediators of aerobic glycolysis and lactate dehydrogenase isoform levels. Meanwhile, CKB overexpression did increase resistance to doxorubicin. TGF-β-induced Smad phosphorylation and Smad-dependent transcriptional activity were significantly up-regulated by CKB expression without changes in inhibitory Smad protein levels. Moreover, treatment with TGF-β considerably enhanced cell viability during doxorubicin treatment and decreased doxorubicin-induced apoptosis in CKB-expressing MDA-MB-231 cells compared to control cells. These results suggest that CKB attenuates doxorubicin-induced apoptosis and potentiates resistance to doxorubicin by enhancing TGF-β signaling in MDA-MB-231 cells.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9586670&blobtype=pdf
Page Count	11
ISSN	19768354
Journal	Animal Cells and Systems [Anim Cells Syst (Seoul)]
Volume Number	26
DOI	10.1080/19768354.2022.2107070
PubMed Central reference number	PMC9586670
Issue Number	5
PubMed reference number	36275445
e-ISSN	21512485
Language	English
Publisher	Taylor & Francis
Publisher Date	2022-08-31
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
Subject Keyword	Apoptosis brain type of creatine kinase (CKB) doxorubicin MDA-MB-231 transforming growth factor-β (TGF-β)
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Animal Science and Zoology