ArticleThe Journal of investigative dermatology2015
MITF Modulates Therapeutic Resistance through EGFR Signaling.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry.Frontiers in oncology · 2022Pooled it
- Article
- PTRF Confers Melanoma-Acquired Drug Resistance Through the Upregulation of EGFR.Cell proliferation · 2026Article
- LINC00313 promotes the aggressiveness and tumorigenesis of cholangiocarcinoma through targeting miR-320b and MITF.Discover oncology · 2025Article
- Acquired resistance to immune checkpoint therapy is caused by glycoprotein non-metastatic melanoma protein B signal cascade.Communications medicine · 2025Article
- Clonal differences underlie variable responses to sequential and prolonged treatment.Cell systems · 2024Article
- The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors.Cell death & disease · 2024Article
- Article
- Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors.Frontiers in immunology · 2024Article
- Drug dependence in cancer is exploitable by optimally constructed treatment holidays.Nature ecology & evolution · 2024Article
- Disrupting cellular memory to overcome drug resistance.Nature communications · 2023Article
- In Silico Studies of Novel Vemurafenib Derivatives as BRAF Kinase Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Review
- The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma.Molecular oncology · 2022Review
- Article
- Article
- Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling.International journal of molecular sciences · 2021Article
- NRF2 Enables EGFR Signaling in Melanoma Cells.International journal of molecular sciences · 2021Article
- Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signalling.Nature communications · 2021Article
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Response to targeted therapies varies significantly despite shared oncogenic mutations. Nowhere is this more apparent than in BRAF (V600E)-mutated melanomas where initial drug response can be striking and yet relapse is commonplace. Resistance to BRAF inhibitors have been attributed to the activation of various receptor tyrosine kinases (RTKs), although the underlying mechanisms have been largely uncharacterized. Here, we found that EGFR-induced vemurafenib resistance is ligand dependent. We employed whole-genome expression analysis and discovered that vemurafenib resistance correlated with the loss of microphthalmia-associated transcription factor (MITF), along with its melanocyte lineage program, and with the activation of EGFR signaling. An inverse relationship between MITF, vemurafenib resistance, and EGFR was then observed in patient samples of recurrent melanoma and was conserved across melanoma cell lines and patients' tumor specimens. Functional studies revealed that MITF depletion activated EGFR signaling and consequently recapitulated the resistance phenotype. In contrast, forced expression of MITF in melanoma and colon cancer cells inhibited EGFR and conferred sensitivity to BRAF/MEK inhibitors. These findings indicate that an "autocrine drug resistance loop" is suppressed by melanocyte lineage signal(s), such as MITF. This resistance loop modulates drug response and could explain the unique sensitivity of melanomas to BRAF inhibition.
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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.