Evidence map›Paper›PMID 32486420›Full record

ArticleCancers2020

The Recombinant Fragment of Human κ-Casein Induces Cell Death by Targeting the Proteins of Mitochondrial Import in Breast Cancer Cells.

Max Richter, Fabian Wohlfromm, Thilo Kähne, Hannes Bongartz, Kamil Seyrek, Yuriy Kit, Olga Chinak, Vladimir A Richter, Olga A Koval, Inna N Lavrik

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Failure to Guard: Mitochondrial Protein Quality Control in Cancer.International journal of molecular sciences · 2021
    Review
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Max RichterTranslational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39120 Magdeburg, Germany.
Fabian WohlfrommTranslational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39120 Magdeburg, Germany.
Thilo KähneInstitute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
Hannes BongartzInstitute of Biology, Systems Biology, Faculty of Natural Sciences, Otto von Guericke University, 39106 Magdeburg, Germany.
Kamil SeyrekTranslational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39120 Magdeburg, Germany.
Yuriy KitDepartment of Regulation of Cell Proliferation, Institute of Cell Biology, 79005 L'viv, Ukraine.ORCID 0000-0002-5995-4381
Olga ChinakDepartment of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk 630090, Russia.
Vladimir A RichterDepartment of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk 630090, Russia.
Olga A KovalDepartment of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk 630090, Russia.ORCID 0000-0001-7788-2249
Inna N LavrikTranslational Inflammation Research, Medical Faculty, Center of Dynamic Systems (CDS), Otto von Guericke University, 39120 Magdeburg, Germany.
Otto-von-Guericke-Universität Magdeburg · DEInstitute of Chemical Biology and Fundamental Medicine · RUInstitute of Cell Biology · UA

Funding

Deutsche Forschungsgemeinschaft LA2386European Regional Development Fund CDSVolkswagen Foundation 90135Wilhelm Sander-Stiftung 2017.009.01
6 · The paper itself

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.

Indexed as

breast cancercell deathlactaptinmitochondriaRL2TOM70κ-Casein

Identifiers

PMID32486420
PMCPMC7352597
OpenAlexW3030862533

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.