Evidence map›Paper›PMID 26119931›Full record

ArticleOncogene2016

Regulation of CD44E by DARPP-32-dependent activation of SRp20 splicing factor in gastric tumorigenesis.

S Zhu, Z Chen, A Katsha, J Hong, A Belkhiri, W El-Rifai

Open access · bronzeAbstract read
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Oncogenic SRSF3 in health and diseases.International journal of biological sciences · 2023
    Review
  6. Identification of prognostic alternative splicing signature in gastric cancer.Archives of public health = Archives belges de sante publique · 2022
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  19. Article
  20. Article
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 1 institution in 1 country.

S ZhuDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Z ChenDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
A KatshaDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
J HongDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
A BelkhiriDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
W El-RifaiDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Targets of Gene Overexpression at 17q in Gastric Tumorigenesis: Darpp32R01CA093999 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI EL-RIFAI, WAEL · 2002 to 2017
$4.5M
BLRD Research Career Scientist Award ApplicationIK6BX003787 · VA · VETERANS HEALTH ADMINISTRATION · PI WAEL EL-RIFAI · 2017 to 2026
–
BLRD VA IK6 BX003787NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NCI NIH HHS P50 CA095103NCI NIH HHS R01 CA093999NCI NIH HHS R01CA93999NIDDK NIH HHS DK058404NIDDK NIH HHS P30 DK058404
6 · The paper itself

Abstract

CD44E is a frequently overexpressed variant of CD44 in gastric cancer. Mechanisms that regulate CD44 splicing and expression in gastric cancer remain unknown. Herein, we investigated the role of DARPP-32 (dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000) in promoting tumor growth through regulation of CD44 splicing. Using western blot and quantitative real-time PCR analysis, our results indicated that knockdown of endogenous DARPP-32 markedly reduces the expression of CD44 V8-V10 (CD44E). Using a quantitative splicing luciferase reporter system, we detected a significant increase in the reporter activity following DARPP-32 overexpression (P<0.001). Conversely, knocking down endogenous DARPP-32 significantly attenuated the splicing activity (P<0.001). Further experiments showed that DARPP-32 regulates the expression of SRp20 splicing factor and co-exists with it in the same protein complex. Inhibition of alternative splicing with digitoxin followed by immunoprecipitation and immunoblotting indicated that DARPP-32 has an important role in regulating SRp20 protein stability. The knockdown of endogenous DARPP-32 confirmed that DARPP-32 regulates the SRp20-dependent CD44E splicing. Using tumor xenograft mouse model, knocking down endogenous DARPP-32 markedly reduced SRp20 and CD44E protein levels with a decreased tumor growth. The reconstitution of SRp20 expression in these cells rescued tumor growth. In addition, we also demonstrated frequent co-overexpression and positive correlation of DARPP-32, SRp20 and CD44E expression levels in human gastric primary tumors. Our novel findings establish for the first time the role of DARPP-32 in regulating splicing factors in gastric cancer cells. The DARPP-32-SRp20 axis has a key role in regulating the CD44E splice variant that promotes gastric tumorigenesis.

Indexed as

Alternative SplicingAnimalsCarcinogenesisCell Line, TumorCell ProliferationDopamine and cAMP-Regulated Phosphoprotein 32Gene Expression Regulation, NeoplasticHumansHyaluronan ReceptorsMiceRNA-Binding ProteinsSerine-Arginine Splicing FactorsSignal TransductionStomach NeoplasmsXenograft Model Antitumor AssaysCD44 protein, humanDopamine and cAMP-Regulated Phosphoprotein 32Hyaluronan ReceptorsPPP1R1B protein, humanRNA-Binding ProteinsSerine-Arginine Splicing FactorsSRSF3 protein, human

Identifiers

PMID26119931
PMCPMC4486340
OpenAlexW1594148199

What OpenQuestion holds

Textmetadata
LicenceTDM
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.