Evidence map›Paper›PMID 21285511›Full record

ArticleThe Journal of clinical investigation2011

An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers.

Terence K Lee, Saravana R K Murthy, Niamh X Cawley, Savita Dhanvantari, Stephen M Hewitt, Hong Lou, Tracy Lau, Stephanie Ma, Thanh Huynh, Robert A Wesley and 4 more

RetractedOpen access · greenAbstract readRetracted Publication
In one paragraph

Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. qPCR primer design revisited.Biomolecular detection and quantification · 2017
    Review
  9. Review
  10. Article
  11. Carboxypeptidase E is a prediction marker for tumor recurrence in early-stage hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. [Screening of Highly Expressed CPEΔN Lung Cancer H1299 Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2015
    Article
  17. Review
  18. Article
  19. Downregulation of CPE regulates cell proliferation and chemosensitivity in pancreatic cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 4 countries.

Terence K LeeDepartment of Surgery, University of Hong Kong, Pokfulam, Hong Kong, China.
Saravana R K Murthy
Niamh X Cawley
Savita Dhanvantari
Stephen M Hewitt
Hong Lou
Tracy Lau
Stephanie Ma
Thanh Huynh
Robert A Wesley
Irene O Ng
Karel Pacak
Ronnie T Poon
Y Peng Loh
National Institutes of Health · USCenter for Cancer Research · USInstitute of Cell Biology and Neurobiology · ITLawson Health Research Institute · CAUniversity of Hong Kong · HK

Funding

Diagnosis, Pathophysiology And Molecular Biology of Pheochromocytoma and ParagangliomaZIAHD008735 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PACAK, KAREL · 2009 to 2024
$28.4M
The Role of Carboxypeptidase E in CancerZIAHD008804 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LOH, YOKE PENG · 2009 to 2019
$6.1M
Tissue Array Research ProgramZICBC010923 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2009 to 2014
$4.7M
Intramural NIH HHS
6 · The paper itself

Abstract

Metastasis is a major cause of mortality in cancer patients. However, the mechanisms governing the metastatic process remain elusive, and few accurate biomarkers exist for predicting whether metastasis will occur, something that would be invaluable for guiding therapy. We report here that the carboxypeptidase E gene (CPE) is alternatively spliced in human tumors to yield an N-terminal truncated protein (CPE-ΔN) that drives metastasis. mRNA encoding CPE-ΔN was found to be elevated in human metastatic colon, breast, and hepatocellular carcinoma (HCC) cell lines. In HCC cells, cytosolic CPE-ΔN was translocated to the nucleus and interacted with histone deacetylase 1/2 to upregulate expression of the gene encoding neural precursor cell expressed, developmentally downregulated gene 9 (Nedd9)--which has been shown to promote melanoma metastasis. Nedd9 upregulation resulted in enhanced in vitro proliferation and invasion. Quantification of mRNA encoding CPE-ΔN in HCC patient samples predicted intrahepatic metastasis with high sensitivity and specificity, independent of cancer stage. Similarly, high CPE-ΔN mRNA copy numbers in resected pheochromocytomas/paragangliomas (PHEOs/PGLs), rare neuroendocrine tumors, accurately predicted future metastasis or recurrence. Thus, CPE-ΔN induces tumor metastasis and should be investigated as a potentially powerful biomarker for predicting future metastasis and recurrence in HCC and PHEO/PGL patients.

Indexed as

Gene Expression Regulation, NeoplasticAdaptor Proteins, Signal TransducingAlternative SplicingBiomarkers, TumorCarboxypeptidase HCell Line, TumorCytosolFemaleHumansMaleMiddle AgedNeoplasm InvasivenessNeoplasm MetastasisParagangliomaPheochromocytomaPhosphoproteinsAdaptor Proteins, Signal TransducingBiomarkers, TumorCarboxypeptidase HNEDD9 protein, humanPhosphoproteinsProtein Isoforms

Identifiers

PMID21285511
PMCPMC3049392
OpenAlexW2061188756

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.