Evidence map›Paper›PMID 38964729›Full record

ArticleCancer letters2024

Secretory Trefoil Factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in Pancreatic Ductal Adenocarcinoma.

Ashu Shah, Rahat Jahan, Sophia G Kisling, Pranita Atri, Gopalakrishnan Natarajan, Palanisamy Nallasamy, Jesse L Cox, Muzafar A Macha, Ishfaq Ahmad Sheikh, Moorthy P Ponnusamy and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Review
  3. Article
  4. 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

12 authors.

Ashu ShahDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Rahat JahanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Sophia G KislingDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Pranita AtriDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Gopalakrishnan NatarajanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Jesse L CoxDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA.
Muzafar A MachaWatson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Kashmir, India.
Ishfaq Ahmad SheikhKing Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198-5950, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, 68198-5950, USA.
Sushil KumarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198-5950, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, 68198-5950, USA. Electronic address: sbatra@unmc.edu.

Funding

Pancreatic Cancer Detection ConsortiumU01CA210240 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Michael A. Hollingsworth · 2017 to 2026
$12.9M
Validation of biomarkers for risk prediction and early diagnosis of Pancreatic AdenocarcinomaU01CA200466 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Surinder K. Batra, Randall Brand · 2016 to 2026
$11.3M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Molecular Imaging Probe(s) for Optical Surgical Navigation of Pancreatic CancerR01CA256973 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Surinder K. Batra, Michael Bouvet · 2022 to 2026
$2.2M
Novel Therapy to Inhibit IPMN ProgressionR01CA263575 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI BATRA, SURINDER K., MALAFA, MOKENGE P. · 2022 to 2024
$2.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Targeting CXCR2 axis in Pancreatic CancerR01CA228524 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SINGH, RAKESH K · 2018 to 2022
$2.0M
NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA210637NCI NIH HHS R01 CA228524NCI NIH HHS R01 CA256973NCI NIH HHS R01 CA263575NCI NIH HHS U01 CA200466NCI NIH HHS U01 CA210240
6 · The paper itself

Abstract

Gemcitabine is the first-line treatment option for patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). However, the frequent adoption of resistance to gemcitabine by cancer cells poses a significant challenge in treating this aggressive disease. In this study, we focused on analyzing the role of trefoil factor 1 (TFF1) in gemcitabine resistance in PDAC. Analysis of PDAC TCGA and cell line datasets indicated an enrichment of TFF1 in the gemcitabine-resistant classical subtype and suggested an inverse correlation between TFF1 expression and sensitivity to gemcitabine treatment. The genetic ablation of TFF1 in PDAC cells enhanced their sensitivity to gemcitabine treatment in both in vitro and in vivo tumor xenografts. The biochemical studies revealed that TFF1 contributes to gemcitabine resistance through enhanced stemness, increasing migration ability of cancer cells, and induction of anti-apoptotic genes. We further pursued studies to predict possible receptors exerting TFF1-mediated gemcitabine resistance. Protein-protein docking investigations with BioLuminate software revealed that TFF1 binds to the chemokine receptor CXCR4, which was supported by real-time binding analysis of TFF1 and CXCR4 using SPR studies. The exogenous addition of TFF1 increased the proliferation and migration of PDAC cells through the pAkt/pERK axis, which was abrogated by treatment with a CXCR4-specific antagonist AMD3100. Overall, the present study demonstrates the contribution of the TFF1-CXCR4 axis in imparting gemcitabine resistance properties to PDAC cells.

Indexed as

Antimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalDeoxycytidineDrug Resistance, NeoplasmGemcitabinePancreatic NeoplasmsReceptors, CXCR4Trefoil Factor-1Xenograft Model Antitumor AssaysAnimalsApoptosisCell Line, TumorCell MovementCell ProliferationHumansMiceAntimetabolites, AntineoplasticCXCR4 protein, humanDeoxycytidineGemcitabineReceptors, CXCR4TFF1 protein, humanTrefoil Factor-1Tumor Suppressor ProteinsApoptosisChemoresistanceCXCR4Gemcitabine resistanceTFF1Trefoil factor

Identifiers

PMID38964729
PMCPMC11804849

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Registered trials

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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.