Evidence map›Paper›PMID 26234680›Full record

ArticleOncogene2016

Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells.

S Calabretta, P Bielli, I Passacantilli, E Pilozzi, V Fendrich, G Capurso, G Delle Fave, C Sette

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
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 160 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 2 pooled it
6.0field-weighted citation impact, top 3% 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

160 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.

  1. Pooled it
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  15. PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential.Journal of cellular and molecular medicine · 2025
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100 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 2 countries.

S CalabrettaDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
P BielliLaboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.
I PassacantilliDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
E PilozziDepartment of Clinic and Molecular Medicine, University of Rome La Sapienza, Rome, Italy.
V FendrichDepartment of Surgery, Philipps-University Marburg, Marburg, Germany.
G CapursoDepartment of Science Medical/Chirurgic and Translational Medicine, University of Rome La Sapienza, Rome, Italy.
G Delle FaveDepartment of Science Medical/Chirurgic and Translational Medicine, University of Rome La Sapienza, Rome, Italy.
C SetteDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Sapienza University of Rome · ITUniversity of Rome Tor Vergata · ITFondazione Santa Lucia · ITPhilipps University of Marburg · DE

Funding

Worldwide Cancer Research 12-0150
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing (AS) of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence-free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favor the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, upregulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to upregulation of PTBP1 and modulation of PKM AS in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.

Indexed as

Alternative SplicingAntimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalCell Line, TumorDeoxycytidineDisease-Free SurvivalDrug Resistance, NeoplasmGemcitabineHeterogeneous-Nuclear RibonucleoproteinsHumansPancreatic NeoplasmsPolypyrimidine Tract-Binding ProteinPyruvate KinaseAntimetabolites, AntineoplasticDeoxycytidineGemcitabineHeterogeneous-Nuclear RibonucleoproteinsPolypyrimidine Tract-Binding ProteinPTBP1 protein, humanPyruvate Kinase

Identifiers

PMID26234680
PMCPMC4650269
OpenAlexW1829491214

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.