Evidence map›Paper›PMID 24830724›Full record

ArticleCancer research2014

The TGFβ-miR200-MIG6 pathway orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors.

Evgeny Izumchenko, Xiaofei Chang, Christina Michailidi, Luciane Kagohara, Rajani Ravi, Keren Paz, Mariana Brait, Mohammad O Hoque, Shizhang Ling, Atul Bedi and 1 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer research, 2014. 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 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
7.8field-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

73 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
  2. Article
  3. Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. ErbBs in Lens Cell Fibrosis and Secondary Cataract.Investigative ophthalmology & visual science · 2023
    Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Evgeny IzumchenkoAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Xiaofei ChangAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Christina MichailidiAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Luciane KagoharaAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Rajani RaviAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Keren PazChampions Oncology, Inc., Baltimore, Maryland.
Mariana BraitAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Mohammad O HoqueAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Shizhang LingAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
Atul BediAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and.
David SidranskyAuthors' Affiliations: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; and dsidrans@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USChampions Oncology (United States) · US

Funding

INTEGRATED DEVELOPMENT OF NOVEL MOLECULAR MARKERSU01CA084986 · NCI · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 1999 to 2014
$33.8M
TARGETING EARLY CHANGES FOR NEW SCREENING STRATEGIESP50CA058184 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 1992 to 2013
$30.5M
TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2007 to 2016
$27.1M
Molecular progression model for HNSCCR37DE012588 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2004 to 2012
$3.3M
NCI NIH HHS P50 CA058184NCI NIH HHS U01 CA084986NCI NIH HHS U01CA084986NIDCR NIH HHS P50 DE019032NIDCR NIH HHS R37 DE012588NIDCR NIH HHS R37DE012588
6 · The paper itself

Abstract

Although specific mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) identify tumors that are responsive to EGFR tyrosine kinase inhibitors (TKI), these genetic alterations are present in only a minority of patients. Patients with tumors expressing wild-type EGFR lack reliable predictive markers of their clinical response to EGFR TKIs. Although epithelial-mesenchymal transition (EMT) has been inversely correlated with the response of cancers to EGFR-targeted therapy, the precise molecular mechanisms underlying this association have not been defined and no specific EMT-associated biomarker of clinical benefit has been identified. Here, we show that during transforming growth factor β (TGFβ)-mediated EMT, inhibition of the microRNAs 200 (miR200) family results in upregulated expression of the mitogen-inducible gene 6 (MIG6), a negative regulator of EGFR. The MIG6-mediated reduction of EGFR occurs concomitantly with a TGFβ-induced EMT-associated kinase switch of tumor cells to an AKT-activated EGFR-independent state. In a panel of 25 cancer cell lines of different tissue origins, we find that the ratio of the expression levels of MIG6 and miR200c is highly correlated with EMT and resistance to erlotinib. Analyses of primary tumor xenografts of patient-derived lung and pancreatic cancers carrying wild-type EGFR showed that the tumor MIG6(mRNA)/miR200 ratio was inversely correlated with response to erlotinib in vivo. Our data demonstrate that the TGFβ-miR200-MIG6 network orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors, and identify a low ratio of MIG6 to miR200 as a promising predictive biomarker of the response of tumors to EGFR TKIs.

Indexed as

Drug Resistance, NeoplasmEpithelial-Mesenchymal TransitionAdaptor Proteins, Signal TransducingAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalEnzyme ActivationErbB ReceptorsGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceMicroRNAsOrgan SpecificityPancreatic NeoplasmsAdaptor Proteins, Signal TransducingAntineoplastic AgentsErbB ReceptorsERRFI1 protein, humanMicroRNAsMIRN200 microRNA, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTransforming Growth Factor betaTumor Suppressor Proteins

Identifiers

PMID24830724
PMCPMC4122100
OpenAlexW2107312379

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.