Evidence map›Paper›PMID 25823819›Full record

ArticleOncotarget2015

ANO1/TMEM16A interacts with EGFR and correlates with sensitivity to EGFR-targeting therapy in head and neck cancer.

Anke Bill, Abraham Gutierrez, Sucheta Kulkarni, Carolyn Kemp, Debora Bonenfant, Hans Voshol, Umamaheswar Duvvuri, L Alex Gaither

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
3.8field-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

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. TMEM16 proteins: CaInternational journal of molecular medicine · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

13 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

8 authors at 5 institutions in 2 countries.

Anke BillNovartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Abraham GutierrezNovartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Sucheta KulkarniUniversity of Pittsburgh, Medical Center, Department of Otolaryngology, Pittsburgh, PA 15213, USA.
Carolyn KempUniversity of Pittsburgh, Medical Center, Department of Otolaryngology, Pittsburgh, PA 15213, USA.
Debora BonenfantNovartis Institutes for Biomedical Research, Basel, CH-4002, Switzerland.
Hans VosholNovartis Institutes for Biomedical Research, Basel, CH-4002, Switzerland.
Umamaheswar DuvvuriUniversity of Pittsburgh, Medical Center, Department of Otolaryngology, Pittsburgh, PA 15213, USA.
L Alex GaitherNovartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Novartis (United States) · USUniversity of Pittsburgh Medical Center · USNovartis Institutes for BioMedical ResearchNovartis (Switzerland) · CHVA Pittsburgh Healthcare System · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The epidermal growth factor receptor (EGFR) contributes to the pathogenesis of head&neck squamous cell carcinoma (HNSCC). However, only a subset of HNSCC patients benefit from anti-EGFR targeted therapy. By performing an unbiased proteomics screen, we found that the calcium-activated chloride channel ANO1 interacts with EGFR and facilitates EGFR-signaling in HNSCC. Using structural mutants of EGFR and ANO1 we identified the trans/juxtamembrane domain of EGFR to be critical for the interaction with ANO1. Our results show that ANO1 and EGFR form a functional complex that jointly regulates HNSCC cell proliferation. Expression of ANO1 affected EGFR stability, while EGFR-signaling elevated ANO1 protein levels, establishing a functional and regulatory link between ANO1 and EGFR. Co-inhibition of EGFR and ANO1 had an additive effect on HNSCC cell proliferation, suggesting that co-targeting of ANO1 and EGFR could enhance the clinical potential of EGFR-targeted therapy in HNSCC and might circumvent the development of resistance to single agent therapy. HNSCC cell lines with amplification and high expression of ANO1 showed enhanced sensitivity to Gefitinib, suggesting ANO1 overexpression as a predictive marker for the response to EGFR-targeting agents in HNSCC therapy. Taken together, our results introduce ANO1 as a promising target and/or biomarker for EGFR-directed therapy in HNSCC.

Indexed as

Anoctamin-1Carcinoma, Squamous CellCell Line, TumorCell ProliferationChloride ChannelsErbB ReceptorsFusion Regulatory Protein 1, Heavy ChainGefitinibHead and Neck NeoplasmsHEK293 CellsHumansMultiprotein ComplexesMutationNeoplasm ProteinsProtein Kinase InhibitorsProtein Structure, TertiaryANO1 protein, humanAnoctamin-1Chloride ChannelsEGFR protein, humanErbB ReceptorsFusion Regulatory Protein 1, Heavy ChainGefitinibMultiprotein ComplexesNeoplasm ProteinsProtein Kinase InhibitorsQuinazolinesRNA, Small InterferingSLC3A2 protein, humanbiomarkercalcium-activated chloride channelEGFR-targeted therapyepidermal growth factor receptor (EGFR)protein-protein interaction

Identifiers

PMID25823819
PMCPMC4496210
OpenAlexW2159814827

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.