Evidence map›Paper›PMID 23874958›Full record

ArticlePloS one2013

S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma.

Ali Khammanivong, Chengxing Wang, Brent S Sorenson, Karen F Ross, Mark C Herzberg

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 51 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 1 institution in 1 country.

Ali KhammanivongDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
Chengxing Wang
Brent S Sorenson
Karen F Ross
Mark C Herzberg
University of Minnesota · US

Funding

MINNESOTA PAIN RESEARCH TRAINING PROGRAMT32DE007288 · NIDCR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HERZBERG, MARK C · 1996 to 2011
$8.8M
INNATE INTRAEPITHELIAL DEFENSE AGAINST ORAL INFECTIONR01DE011831 · NIDCR · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HERZBERG, MARK C · 1997 to 2006
$2.0M
Intracellular Calprotectin in the Cell-Autonomous Defense of the Oral MucosaF30DE020210 · NIDCR · UNIVERSITY OF MINNESOTA · PI SORENSON, BRENT S · 2009 to 2013
$206k
NIDCR NIH HHS F30 DE020210NIDCR NIH HHS F30DE020210NIDCR NIH HHS R01 DE011831NIDCR NIH HHS R01DE11831NIDCR NIH HHS T32 DE007288NIDCR NIH HHS T32DE007288
6 · The paper itself

Abstract

Malignant transformation results in abnormal cell cycle regulation and uncontrolled growth in head and neck squamous cell carcinoma (HNSCC) and other cancers. S100A8/A9 (calprotectin) is a calcium-binding heterodimeric protein complex implicated in cell cycle regulation, but the specific mechanism and role in cell cycle control and carcinoma growth are not well understood. In HNSCC, S100A8/A9 is downregulated at both mRNA and protein levels. We now report that downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control and increased growth of carcinoma cells. To show its role in carcinogenesis in an in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human carcinoma cell line (KB cells, HeLa-like). S100A8/A9 expression increases PP2A phosphatase activity and p-Chk1 (Ser345) phosphorylation, which appears to signal inhibitory phosphorylation of mitotic p-Cdc25C (Ser216) and p-Cdc2 (Thr14/Tyr15) to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell division. As expected, S100A8/A9-expressing cells show both decreased anchorage-dependent and -independent growth and mitotic progression. Using shRNA, silencing of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2 (Thr14/Tyr14) level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9-mediated control of the G2/M cell cycle checkpoint is, therefore, a likely suppressive mechanism in human squamous cell carcinomas and may suggest new therapeutic approaches.

Indexed as

Calgranulin ACalgranulin BCarcinoma, Squamous CellCell DivisionCell Line, TumorCell ProliferationG2 PhaseG2 Phase Cell Cycle CheckpointsGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansModels, BiologicalProtein BindingProtein Phosphatase 2Signal TransductionSquamous Cell Carcinoma of Head and NeckCalgranulin ACalgranulin BProtein Phosphatase 2

Identifiers

PMID23874958
PMCPMC3706396
OpenAlexW1995829023

What OpenQuestion holds

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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.