Evidence map›Paper›PMID 27863429›Full record

ArticleOncotarget2017

Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness.

Tao Zhang, Xiaopei Shen, Rengyun Liu, Guangwu Zhu, Justin Bishop, Mingzhao Xing

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 23% 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

12 citing papers in PubMed, 18 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

6 authors at 2 institutions in 1 country.

Tao ZhangLaboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Xiaopei ShenLaboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Rengyun LiuLaboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Guangwu ZhuLaboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Justin BishopDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Mingzhao XingLaboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Genetic & Epigenetic Events in Papillary Thyroid CancerR01CA113507 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2006 to 2015
$2.2M
TERT Promoter Mutations in Thyroid CancerR01CA189224 · NCI · JOHNS HOPKINS UNIVERSITY · PI XING, MICHAEL MINGZHAO · 2015 to 2019
$1.8M
NCI NIH HHS R01 CA113507NCI NIH HHS R01 CA189224
6 · The paper itself

Abstract

How the BRAF V600E mutation promotes the pathogenesis and aggressiveness of papillary thyroid cancer (PTC) is not completely understood. Here we explored a novel mechanism involving WASP interacting protein family member 1 (WIPF1). In PTC tumors, compared with the wild-type BRAF, BRAF V600E was associated with over-expression and hypomethylation of the WIPF1 gene. In thyroid cancer cell lines with wild-type BRAF, WIPF1 expression was robustly upregulated upon introduced expression of BRAF V600E (P=0.03) whereas the opposite was seen upon BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E. Methylation of a functionally critical region of the WIPF1 promoter was decreased by expressing BRAF V600E in cells harboring the wild-type BRAF and increased by BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E mutation. Under-expression and hypermethylation of WIPF1 induced by stable BRAF knockdown was reversed by DNA demethylating agent 5'-azadeoxycytidine. Knockdown of WIPF1 robustly inhibited anchorage-independent colony formation, migration, and invasion of thyroid cancer cells and suppressed xenograft thyroid cancer tumor growth and vascular invasion, mimicking the effects of BRAF knockdown. In human PTC tumors, WIPF1 expression was associated with extrathyroidal invasion (P=0.01) and lymph node metastasis (P=2.64E-05). In summary, BRAF V600E-activated MAP kinase pathway causes hypomethylation and overexpression of WIPF1; WIPF1 then functions like an oncoprotein to robustly promote aggressive cellular and tumor behaviors of PTC. This represents a novel mechanism in BRAF V600E-promoted PTC aggressiveness and identifies WIPF1 as a novel therapeutic target for thyroid cancer.

Indexed as

Epigenesis, GeneticGene Expression Regulation, NeoplasticMutationAnimalsCarcinoma, PapillaryCell Line, TumorCell MovementCell ProliferationCytoskeletal ProteinsDisease Models, AnimalDisease ProgressionDNA MethylationFemaleGene ExpressionGene Knockdown TechniquesGenes, ReporterCytoskeletal ProteinsIntracellular Signaling Peptides and ProteinsProto-Oncogene Proteins B-rafWIPF1 protein, humanBRAF V600Eoncogenesisthyroid cancertumor aggressivenessWIPF1

Identifiers

PMID27863429
PMCPMC5352205
OpenAlexW2555072314

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.