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Title: The recombinant fragment of human [kappa]-casein induces cell death by targeting the proteins of mitochondrial import in breast cancer cells
Author(s): Richter, Max
Wohlfromm, Fabian
Kähne, Thilo
Bongartz, HannesLook up in the Integrated Authority File of the German National Library
Seyrek, Kamil
Kit, Yuriy
Chinak, Olga
Richter, Vladimir A.
Koval, Olga A.
Lavrik, Inna N.Look up in the Integrated Authority File of the German National Library
Issue Date: 2020
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-367071
Subjects: Breast cancer
Cell death
Abstract: Breast cancer is still one of the most common cancers for women. Specified therapeutics are indispensable for optimal treatment. In previous studies, it has been shown that RL2, the recombinant fragment of human κ-Casein, induces cell death in breast cancer cells. However, the molecular mechanisms of RL2-induced cell death remain largely unknown. In this study, mechanisms of RL2-induced cell death in breast cancer cells were systematically investigated. In particular, we demonstrate that RL2 induces loss of mitochondrial membrane potential and cellular ATP loss followed by cell death in breast cancer cells. The mass spectrometry-based screen for RL2 interaction partners identified mitochondrial import protein TOM70 as a target of RL2, which was subsequently validated. Further to this, we show that RL2 is targeted to mitochondria after internalization into the cells, where it can also be found in the dimeric form. The importance of TOM70 and RL2 interaction in RL2-induced reduction in ATP levels was validated by siRNA-induced downregulation of TOM70, resulting in the partial rescue of ATP production. Taken together, this study demonstrates that RL2–TOM70 interaction plays a key role in RL2-mediated cell death and targeting this pathway may provide new therapeutic options for treating breast cancer.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: DFG-Publikationsfonds 2020
Journal Title: Cancers
Publisher: MDPI
Publisher Place: Basel
Volume: 12
Issue: 6
Original Publication: 10.3390/cancers12061427
Page Start: 1
Page End: 21
Appears in Collections:Medizinische Fakultät (OA)

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