Evidence map›Paper›PMID 26278961›Full record

ArticleScientific reports2015

Label-free quantitative phosphoproteomics with novel pairwise abundance normalization reveals synergistic RAS and CIP2A signaling.

Otto Kauko, Teemu Daniel Laajala, Mikael Jumppanen, Petteri Hintsanen, Veronika Suni, Pekka Haapaniemi, Garry Corthals, Tero Aittokallio, Jukka Westermarck, Susumu Y Imanishi

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 63 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

10 authors at 4 institutions in 1 country.

Otto Kauko1] Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland [2] Department of Pathology, University of Turku, FI-20520 Turku, Finland [3] Turku Doctoral Program of Biomedical Sciences (TuBS), Turku, Finland.
Teemu Daniel Laajala1] Department of Mathematics and Statistics, University of Turku, FI-20014 Turku, Finland [2] Drug Research Doctoral Programme (DRDP), Turku, Finland.
Mikael JumppanenTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland.
Petteri HintsanenInstitute for Molecular Medicine Finland, Tukholmankatu 8, FI-00290 Helsinki, Finland.
Veronika Suni1] Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland [2] Turku Centre for Computer Science, FI-20520 Turku, Finland.
Pekka HaapaniemiTurku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland.
Garry Corthals1] Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland [2] Van 't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
Tero AittokallioInstitute for Molecular Medicine Finland, Tukholmankatu 8, FI-00290 Helsinki, Finland.
Jukka Westermarck1] Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland [2] Department of Pathology, University of Turku, FI-20520 Turku, Finland.
Susumu Y Imanishi1] Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistokatu 6, FI-20520 Turku, Finland [2] Faculty of Pharmacy, Meijo University, Yagotoyama 150, Tempaku, Nagoya 468-8503, Japan.
University of Turku · FIÅbo Akademi University · FIInstitute for Molecular Medicine Finland · FITurku Centre for Biotechnology · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyperactivated RAS drives progression of many human malignancies. However, oncogenic activity of RAS is dependent on simultaneous inactivation of protein phosphatase 2A (PP2A) activity. Although PP2A is known to regulate some of the RAS effector pathways, it has not been systematically assessed how these proteins functionally interact. Here we have analyzed phosphoproteomes regulated by either RAS or PP2A, by phosphopeptide enrichment followed by mass-spectrometry-based label-free quantification. To allow data normalization in situations where depletion of RAS or PP2A inhibitor CIP2A causes a large uni-directional change in the phosphopeptide abundance, we developed a novel normalization strategy, named pairwise normalization. This normalization is based on adjusting phosphopeptide abundances measured before and after the enrichment. The superior performance of the pairwise normalization was verified by various independent methods. Additionally, we demonstrate how the selected normalization method influences the downstream analyses and interpretation of pathway activities. Consequently, bioinformatics analysis of RAS and CIP2A regulated phosphoproteomes revealed a significant overlap in their functional pathways. This is most likely biologically meaningful as we observed a synergistic survival effect between CIP2A and RAS expression as well as KRAS activating mutations in TCGA pan-cancer data set, and synergistic relationship between CIP2A and KRAS depletion in colony growth assays.

Indexed as

Area Under CurveAutoantigensCell ProliferationChromatography, High Pressure LiquidCluster AnalysisHeLa CellsHumansIntracellular Signaling Peptides and ProteinsKaplan-Meier EstimateMembrane ProteinsNeoplasmsPhosphopeptidesPhosphorylationProtein Phosphatase 2ras ProteinsRNA InterferenceAutoantigensCIP2A protein, humanIntracellular Signaling Peptides and ProteinsMembrane ProteinsPhosphopeptidesProtein Phosphatase 2ras ProteinsRNA, Small InterferingTitaniumtitanium dioxide

Identifiers

PMID26278961
PMCPMC4642524
OpenAlexW2412770710

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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.