Evidence map›Paper›PMID 32188406›Full record

ArticleBMC molecular and cell biology2020

Cathepsin K regulates localization and secretion of Tartrate-Resistant Acid Phosphatase (TRAP) in TRAP-overexpressing MDA-MB-231 breast cancer cells.

Anja Reithmeier, Maria Norgård, Barbro Ek-Rylander, Tuomas Näreoja, Göran Andersson

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC molecular and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Anja ReithmeierDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52, Stockholm, Sweden. anja.reithmeier@ki.se.
Maria NorgårdDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52, Stockholm, Sweden.
Barbro Ek-RylanderDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52, Stockholm, Sweden.
Tuomas NäreojaDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52, Stockholm, Sweden. tuomas.nareoja@ki.se.ORCID http://orcid.org/0000-0002-2174-4434
Göran AnderssonDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52, Stockholm, Sweden.
Karolinska Institutet · SEScience for Life Laboratory · SE

Funding

Cancer and Allergy Foundation 2017Cancerfonden 2016Jane ja Aatos Erkon Säätiö 2017Loo och Hans Ostermans Stiftelse för Medicinsk Forskning 2018Maud Kuistilan Muistosäätiö 2017Vetenskapsrådet #2017-01083Vetenskapsrådet K2015-99X-10363-23-4
6 · The paper itself

Abstract

backgroundTartrate-resistant acid phosphatase (TRAP/ ACP5) belongs to the binuclear metallophosphatase family and is present in two isoforms. The primary translation product is an uncleaved TRAP 5a isoform with low phosphatase activity. TRAP 5a can be post-translationally processed to a cleaved TRAP 5b isoform with high phosphatase activity by e.g. cysteine proteinases, such as Cathepsin K (CtsK). The relevance of the phosphatase activity of TRAP 5b has been demonstrated for proliferation, migration and invasion of cancer cells. TRAP-overexpressing MDA-MB-231 breast cancer cells displayed higher levels of TRAP 5a and efficient processing of TRAP 5a to TRAP 5b protein, but no changes in levels of CtsK when compared to mock-transfected cells. In TRAP-overexpressing cells colocalization of TRAP 5a and proCtsK was augmented, providing a plausible mechanism for generation of TRAP 5b. CtsK expression has been associated with cancer progression and has been pharmacologically targeted in several clinical studies.

resultsIn the current study, CtsK inhibition with MK-0822/Odanacatib did not abrogate the formation of TRAP 5b, but reversibly increased the intracellular levels of a N-terminal fragment of TRAP 5b and reduced secretion of TRAP 5a reversibly. However, MK-0822 treatment neither altered intracellular TRAP activity nor TRAP-dependent cell migration, suggesting involvement of additional proteases in proteolytic processing of TRAP 5a. Notwithstanding, CtsK was shown to be colocalized with TRAP and to be involved in the regulation of secretion of TRAP 5a in a breast cancer cell line, while it still was not essential for processing of TRAP 5a to TRAP 5b isoform.

conclusionIn cancer cells multiple proteases are involved in cleaving TRAP 5a to high-activity phosphatase TRAP 5b. However, CtsK-inhibiting treatment was able to reduce secretion TRAP 5a from TRAP-overexpressing cancer cells.

Indexed as

Cathepsin KTartrate-Resistant Acid PhosphataseBreast NeoplasmsCell Line, TumorFemaleHumansACP5 protein, humanCathepsin KCTSK protein, humanTartrate-Resistant Acid PhosphataseACP5CancerCathepsin KIntracellular traffickingProteolytic processingTartrate-resistant acid phosphatase

Identifiers

PMID32188406
PMCPMC7081696
OpenAlexW3012903378

What OpenQuestion holds

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Registered trials

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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.