Evidence map›Paper›PMID 22389437›Full record

ArticleCancer prevention research (Philadelphia, Pa.)2012

Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma.

Janine G Einspahr, Valerie Calvert, David S Alberts, Clara Curiel-Lewandrowski, James Warneke, Robert Krouse, Steven P Stratton, Lance Liotta, Caterina Longo, Giovanni Pellacani and 7 more

Erratum issuedOpen access · greenAbstract readComparative Study
In one paragraph

Article in Cancer prevention research (Philadelphia, Pa.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

54 citing papers in PubMed, 89 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis.JID innovations : skin science from molecules to population health · 2023
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas.Cellular and molecular life sciences : CMLS · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET Inhibitors in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
    Pellicani, Giovanni [corrected to Pellacani, Giovanni]
5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Janine G EinspahrUniversity of Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA. jeinspahr@azcc.arizona.edu
Valerie Calvert
David S Alberts
Clara Curiel-Lewandrowski
James Warneke
Robert Krouse
Steven P Stratton
Lance Liotta
Caterina Longo
Giovanni Pellacani
Giovanni Pellicani
Anil Prasad
Paul Sagerman
Yira Bermudez
Jianghong Deng
G Timothy Bowden
Emanuel F Petricoin
Ospedale Santa Maria · ITSouthern Arizona VA Health Care System · USGeorge Mason University · USUniversity of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
VITAMIN A, AND ITS PRECURSORS AND DERIVATIVES AS THERAPEUTIC MODALITIESP01CA027502 · NCI · UNIVERSITY OF ARIZONA · PI EINSPAHR, JANINE G · 1985 to 2015
$36.3M
NCI NIH HHS CA023074NCI NIH HHS CA027502NCI NIH HHS P01 CA027502NCI NIH HHS P30 CA023074
6 · The paper itself

Abstract

Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.

Indexed as

Signal TransductionAdolescentAdultAgedAged, 80 and overCarcinoma, Squamous CellDisease ProgressionFemaleHumansLaser Capture MicrodissectionMaleMiddle AgedPhosphorylationPrognosisProspective StudiesSkin

Identifiers

PMID22389437
PMCPMC3297971
OpenAlexW2118593202

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.