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Titel: The recombinant fragment of human [kappa]-casein induces cell death by targeting the proteins of mitochondrial import in breast cancer cells
Autor(en): Richter, Max
Wohlfromm, Fabian
Kähne, Thilo
Bongartz, HannesIn der Gemeinsamen Normdatei der DNB nachschlagen
Seyrek, Kamil
Kit, Yuriy
Chinak, Olga
Richter, Vladimir A.
Koval, Olga A.
Lavrik, Inna N.In der Gemeinsamen Normdatei der DNB nachschlagen
Erscheinungsdatum: 2020
Art: Artikel
Sprache: Englisch
URN: urn:nbn:de:gbv:ma9:1-1981185920-367071
Schlagwörter: Breast cancer
Mitochondria
κ-Casein
Lactaptin,
TOM70
Cell death
Zusammenfassung: 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.
URI: https://opendata.uni-halle.de//handle/1981185920/36707
http://dx.doi.org/10.25673/36475
Open-Access: Open-Access-Publikation
Nutzungslizenz: (CC BY 4.0) Creative Commons Namensnennung 4.0 International(CC BY 4.0) Creative Commons Namensnennung 4.0 International
Sponsor/Geldgeber: DFG-Publikationsfonds 2020
Journal Titel: Cancers
Verlag: MDPI
Verlagsort: Basel
Band: 12
Heft: 6
Originalveröffentlichung: 10.3390/cancers12061427
Seitenanfang: 1
Seitenende: 21
Enthalten in den Sammlungen:Medizinische Fakultät (OA)

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