Evidence map›Paper›PMID 28720574›Full record

ArticleCancer research2017

Fructose-1,6-bisphosphatase Inhibits ERK Activation and Bypasses Gemcitabine Resistance in Pancreatic Cancer by Blocking IQGAP1-MAPK Interaction.

Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.9field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Article
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  8. Article
  9. Review
  10. Lysine acetylation and its role in the pathophysiology of acute pancreatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  11. The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
  12. Review
  13. Article
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5 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

9 authors at 1 institution in 1 country.

Xin JinDepartment of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Yunqian PanDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Liguo WangDepartment of Medical Informatics and Statistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
Tao MaDepartment of Medical Informatics and Statistics, Mayo Clinic College of Medicine, Rochester, Minnesota.
Lizhi ZhangDepartment of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Amy H TangDepartment of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia.
Daniel D BilladeauDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Heshui WuDepartment of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. huang.haojie@mayo.edu heshuiwu@163.com.
Haojie HuangDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota. huang.haojie@mayo.edu heshuiwu@163.com.
Mayo Clinic · US

Funding

Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7M
Role of proinflammatory cytokine-induced AR degradation in castration-resistant prostate cancerR01CA130908 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HUANG, HAOJIE · 2010 to 2021
$3.5M
Role of FOXO1 Inactivation in Prostate TumorigenesisR01CA134514 · NCI · UNIVERSITY OF MINNESOTA · PI HUANG, HAOJIE · 2009 to 2019
$3.3M
Role of RUNX2 in prostate cancer intratumoral androgen synthesis and progressionR01CA193239 · NCI · MAYO CLINIC ROCHESTER · PI HUANG, HAOJIE · 2015 to 2019
$1.8M
SIAH2-Dependent Proteolysis in Cell Migration, Tumor Growth and Cancer MetastasisR01CA140550 · NCI · EASTERN VIRGINIA MEDICAL SCHOOL · PI TANG, AMY H. · 2010 to 2014
$1.4M
Regulated Proteolysis in RAS Signal TransductionR01GM069922 · NIGMS · MAYO CLINIC ROCHESTER · PI TANG, AMY H. · 2004 to 2009
$1.3M
NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA130908NCI NIH HHS R01 CA134514NCI NIH HHS R01 CA140550NCI NIH HHS R01 CA193239NIGMS NIH HHS R01 GM069922
6 · The paper itself

Abstract

Dysregulation of the MAPK pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase-activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and ERK. Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here, we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells. FBP1 binding to the WW domain of IQGAP1 impeded IQGAP1-dependent ERK1/2 phosphorylation (pERK1/2) in a manner independent of FBP1 enzymatic activity. Conversely, decreased FBP1 expression induced pERK1/2 levels in PDAC cell lines and correlated with increased pERK1/2 levels in patient specimens. Treatment with gemcitabine caused undesirable activation of ERK1/2 in PDAC cells, but cotreatment with the FBP1-derived small peptide inhibitor FBP1 E4 overcame gemcitabine-induced ERK activation, thereby increasing the anticancer efficacy of gemcitabine in PDAC. These findings identify a primary mechanism of resistance of PDAC to standard therapy and suggest that the FBP1-IQGAP1-ERK1/2 signaling axis can be targeted for effective treatment of PDAC.

Indexed as

Antimetabolites, AntineoplasticCarcinoma, Pancreatic DuctalCell Line, TumorDeoxycytidineDrug Resistance, NeoplasmFructose-BisphosphataseGemcitabineHumansMAP Kinase Signaling SystemPancreatic Neoplasmsras GTPase-Activating ProteinsSignal TransductionTransfectionAntimetabolites, AntineoplasticDeoxycytidineFructose-BisphosphataseGemcitabineIQ motif containing GTPase activating protein 1ras GTPase-Activating Proteins

Identifiers

PMID28720574
PMCPMC5581962
OpenAlexW2738397042

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.