Evidence map›Paper›PMID 22878588›Full record

ArticleMolecular cancer research : MCR2012

S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

Christopher H Switzer, Sharon A Glynn, Robert Y-S Cheng, Lisa A Ridnour, Jeffrey E Green, Stefan Ambs, David A Wink

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05660083 (Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer), which is not on this map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
7.7field-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.

NCT05660083 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer (MpBC)

TypeinterventionalSponsorThe Methodist Hospital Research InstituteRan2023 to 2028Enrolled36ConditionsHER2-negative Breast Cancer, Metastatic Breast Cancer, Metaplastic Breast Carcinoma, TNBC - Triple-Negative Breast CancerArmsL-NMMA
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 134 citations in OpenAlex.

  1. Review
  2. Review
  3. NO-PDT and chemotherapy: spatiotemporal control to achieve therapeutic synergy.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. The Triple Crown: NO, CO, and HPharmacology & therapeutics · 2023
    Review

24 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

7 authors at 1 institution in 1 country.

Christopher H SwitzerRadiation Biology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Sharon A Glynn
Robert Y-S Cheng
Lisa A Ridnour
Jeffrey E Green
Stefan Ambs
David A Wink
National Cancer Institute · US

Funding

Novel Markers for Disease Outcome in Breast CancerZIABC010887 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI AMBS, STEFAN · 2009 to 2025
$11.5M
Nitric Oxide as a Modifier of Oxidative StressZIASC007281 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WINK, DAVID · 2009 to 2025
$8.1M
Intramural NIH HHS ZIA SC007281PHS HHS 1ZIASC007281-18
6 · The paper itself

Abstract

Increased inducible nitric oxide synthase (NOS2) expression in breast tumors is associated with decreased survival of estrogen receptor negative (ER-) breast cancer patients. We recently communicated the preliminary observation that nitric oxide (NO) signaling results in epidermal growth factor receptor (EGFR) tyrosine phosphorylation. To further define the role of NO in the pathogenesis of ER- breast cancer, we examined the mechanism of NO-induced EGFR activation in human ER- breast cancer. NO was found to activate EGFR and Src by a mechanism that includes S-nitrosylation. NO, at physiologically relevant concentrations, induced an EGFR/Src-mediated activation of oncogenic signal transduction pathways (including c-Myc, Akt, and β-catenin) and the loss of PP2A tumor suppressor activity. In addition, NO signaling increased cellular EMT, expression and activity of COX-2, and chemoresistance to adriamycin and paclitaxel. When connected into a network, these concerted events link NO to the development of a stem cell-like phenotype, resulting in the upregulation of CD44 and STAT3 phosphorylation. Our observations are also consistent with the finding that NOS2 is associated with a basal-like transcription pattern in human breast tumors. These results indicate that the inhibition of NOS2 activity or NO signaling networks may have beneficial effects in treating basal-like breast cancer patients.

Indexed as

Signal TransductionAnimalsBasal Cell Carcinomabeta CateninBreast NeoplasmsCell Line, TumorCoculture TechniquesEpithelial-Mesenchymal TransitionErbB ReceptorsFemaleHumansMacrophagesMiceNitratesNitric OxideNitric Oxide Synthase Type IIbeta CateninEGFR protein, humanErbB ReceptorsMYC protein, humanNitratesNitric OxideNitric Oxide Synthase Type IINitritesNOS2 protein, humanProtein Phosphatase 2Proto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycsrc-Family Kinases

Identifiers

PMID22878588
PMCPMC3463231
OpenAlexW2138950473

What OpenQuestion holds

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Registered trials

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.