Evidence map›Paper›PMID 26330541›Full record

ArticleMolecular & cellular proteomics : MCP2015

Phosphoproteomic Analysis Identifies Focal Adhesion Kinase 2 (FAK2) as a Potential Therapeutic Target for Tamoxifen Resistance in Breast Cancer.

Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Raja Sekhar Nirujogi, Min-Sik Kim, Srikanth S Manda, Vered Stearns, Edward Gabrielson, Saraswati Sukumar, Akhilesh Pandey

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2015. 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
2.2field-weighted citation impact, top 13% 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, 56 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 2 countries.

Xinyan WuFrom the ‡McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;
Muhammad Saddiq ZahariFrom the ‡McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;
Santosh Renuse§Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India;
Raja Sekhar Nirujogi§Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India;
Min-Sik KimFrom the ‡McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;
Srikanth S Manda§Institute of Bioinformatics, International Technology Park, Bangalore, 560066 India;
Vered Stearns¶Department of Oncology;
Edward Gabrielson‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Saraswati Sukumar¶Department of Oncology;
Akhilesh PandeyFrom the ‡McKusick-Nathans Institute of Genetic Medicine and Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; ¶Department of Oncology; ‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 pandey@jhmi.edu.
Institute of Bioinformatics · INJohns Hopkins University · USJohns Hopkins Medicine · USMolecular Oncology (United States) · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Proteome Characterization Center: A Genoproteomics Pipeline for Cance ResearchU24CA160036 · NCI · JOHNS HOPKINS UNIVERSITY · PI CHAN, DANIEL WANYUI, ZHANG, HUI · 2011 to 2016
$10.7M
Networks, Pathways and Dynamics of Lysine ModificationU54GM103520 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BADER, JOEL S. · 2012 to 2013
$7.0M
Personalized Therapy of Hormone Refractory Breast CancerR01CA184165 · NCI · MAYO CLINIC ROCHESTER · PI PANDEY, AKHILESH · 2015 to 2019
$1.8M
NCI NIH HHS CA006973NCI NIH HHS CA184165NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA184165NCI NIH HHS U24 CA160036NCI NIH HHS U24CA160036NHLBI NIH HHS HHSN268201000032CNIGMS NIH HHS U54 GM103520NIGMS NIH HHS U54GM103520PHS HHS HHSN268201000032C
6 · The paper itself

Abstract

Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers.

Indexed as

AdenocarcinomaAnimalsAntineoplastic Agents, HormonalBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmFemaleFocal Adhesion Kinase 2Gene Expression Regulation, NeoplasticHumansIsotope LabelingMCF-7 CellsMiceMice, NudeNeoplasm ProteinsPhosphoproteinsAntineoplastic Agents, HormonalFocal Adhesion Kinase 2Neoplasm ProteinsPhosphoproteinsProteomePTK2B protein, humanReceptors, EstrogenRNA, Small InterferingTamoxifen

Identifiers

PMID26330541
PMCPMC4638033
OpenAlexW2151890505

What OpenQuestion holds

Textmetadata
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.