Evidence map›Paper›PMID 25753158›Full record

ArticleCell research2015

ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer.

Shunrong Ji, Yi Qin, Si Shi, Xiangyuan Liu, Hongli Hu, Hu Zhou, Jing Gao, Bo Zhang, Wenyan Xu, Jiang Liu and 10 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 140 citations in OpenAlex.

  1. Article
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  4. USP10-mediated deubiquitination and activation ofActa pharmaceutica Sinica. B · 2026
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  8. Proteomics in pancreatic cancer.Biomarker research · 2025
    Review
  9. Article
  10. SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  11. Cell signaling inFrontiers in cellular and infection microbiology · 2025
    Review
  12. Article
  13. Article
  14. Review
  15. Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024
    Review
  16. Transcriptional Up-Regulation of FBXW7 by KInternational journal of molecular sciences · 2024
    Article
  17. Article
  18. Article
  19. Review
  20. The mCancers · 2023
    Article

28 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

20 authors at 5 institutions in 2 countries.

Shunrong Ji1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Yi Qin1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Si Shi1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Xiangyuan LiuKey Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Hongli HuKey Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Hu ZhouShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Jing GaoShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Bo Zhang1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Wenyan Xu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Jiang Liu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Dingkong Liang1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Liang Liu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Chen Liu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Jiang Long1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Haijun ZhouDepartment of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Paul J ChiaoDepartment of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jin Xu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Quanxing Ni1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Daming GaoKey Laboratory of System Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xianjun Yu1] Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [3] Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Fudan University Shanghai Cancer Center · CNChinese Academy of Sciences · CNShanghai Medical College of Fudan University · CNThe University of Texas MD Anderson Cancer Center · USCenter for Excellence in Molecular Cell Science · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
6 · The paper itself

Abstract

F-box and WD repeat domain-containing 7 (FBW7) is the substrate recognition component of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex and functions as a major tumor suppressor by targeting various oncoproteins for degradation. Genomic deletion or mutation of FBW7 has frequently been identified in many human cancers but not in pancreatic ductal adenocarcinoma. Thus it is important to know how the tumor suppressive function of FBW7 is impaired in pancreatic cancer. In this study, we first observed that low FBW7 expression correlated significantly with ERK activation in pancreatic cancer clinical samples, primarily due to KRAS mutations in pancreatic cancer. We further showed that ERK directly interacted with FBW7 and phosphorylated FBW7 at Thr205, which sequentially promoted FBW7 ubiquitination and proteasomal degradation. Furthermore, the phospho-deficient T205A FBW7 mutant is resistant to ERK activation and could significantly suppress pancreatic cancer cell proliferation and tumorigenesis. These results collectively demonstrate how the oncogenic KRAS mutation inhibits the tumor suppressor FBW7, thus revealing an important function of KRAS mutations in promoting pancreatic cancer progression.

Indexed as

AnimalsCell Cycle ProteinsCell Line, TumorCell ProliferationExtracellular Signal-Regulated MAP KinasesF-Box ProteinsF-Box-WD Repeat-Containing Protein 7HumansMiceMutationPancreatic NeoplasmsPhosphorylationProteasome Endopeptidase ComplexProtein BindingProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Cell Cycle ProteinsExtracellular Signal-Regulated MAP KinasesF-Box ProteinsF-Box-WD Repeat-Containing Protein 7FBXW7 protein, humanKRAS protein, humanProteasome Endopeptidase ComplexProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras ProteinsUbiquitin-Protein Ligases

Identifiers

PMID25753158
PMCPMC4423074
OpenAlexW2033160470

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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.