Evidence map›Paper›PMID 25323586›Full record

Trial reportCell death and differentiation2015

Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer.

D-W Wu, C-C Huang, S-W Chang, T-H Chen, H Lee

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

29 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026
    Review
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  9. Reposition of the anti-inflammatory drug diacerein in anSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022
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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.

D-W WuGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
C-C Huang1] School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan [2] Division of Colon and Rectum, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
S-W Chang1] School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan [2] Division of Colon and Rectum, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
T-H Chen1] School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan [2] Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
H LeeGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Taipei Medical University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

5-Fluorouracil (5-FU) is chemotherapeutic agent widely used for the treatment of colorectal cancer. Unfortunately, advanced colorectal cancer is often resistance to such chemotherapy and poor outcome. An adaptor protein paxillin (PXN) is phosphorylated at Y31/Y118 (pPXN-Y31/Y118) by Src contributes to cell mobility and Ser (S)272 of PXN in LD4 domain is important to the interaction between PXN and Bcl-2. We thus hypothesized that pPXN-Y31/Y118 may be required for Bcl-2 protein stability via PXN interacting with Bcl-2 to confer 5-FU resistance in colorectal cancer. Mechanistically, pPXN-S272 is phosphorylated through pPXN-Y31/Y118-mediated p21 protein-activated kinase 1 (PAK1) activation and pPXN-S272 is required for PXN to interact with Bcl-2. The interaction between PXN and Bcl-2 is essential for Bcl-2 protein stability through phosphorylation of Bcl-2 at S87 (pBcl-2-S87) by pPXN-Y31/Y118-mediated ERK activation. An increase in Bcl-2 expression by PXN is responsible for resistance to 5-FU. The resistance to 5-FU can be abolished by inhibitor of Src and PAK1 or Bcl-2 antagonist in cell and animal models. Among patients, Bcl-2 expression is positively correlated with expression of PXN and pPXN-S272, respectively. Patients with high PXN/high Bcl-2 or high pPXN-S272/high Bcl-2 tumors are commonly to have an unfavorable response to 5-FU-based chemotherapy, compared with patients who have high PXN, high pPXN-S272 or high Bcl-2 tumors alone. Therefore, we suggest that Src, PAK1 or Bcl-2 inhibitor may potentially overcome the resistance of 5-FU-based chemotherapy and consequently to improve outcomes in patients with PXN/Bcl-2 and pPXN-S272/Bcl-2-positive tumors.

Indexed as

Amino Acid SubstitutionCell Line, TumorColorectal NeoplasmsDrug Resistance, NeoplasmFemaleFluorouracilFollow-Up StudiesGene Expression Regulation, NeoplasticHumansMaleMutation, Missensep21-Activated KinasesPaxillinProto-Oncogene Proteins c-bcl-2Retrospective StudiesBCL2 protein, humanFluorouracilp21-Activated KinasesPAK1 protein, humanPaxillinProto-Oncogene Proteins c-bcl-2PXN protein, human

Identifiers

PMID25323586
PMCPMC4392075
OpenAlexW2038887440

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.