ArticleGenome research2014
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 60 citations in OpenAlex.
- Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex.Cancer discovery · 2017Trial
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- Chromosome 3p deletion leads to extensive genomic alterations in diverse cancers and confers synthetic lethality in uveal melanoma.bioRxiv : the preprint server for biology · 2026Article
- MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species.Scientific reports · 2024Article
- Melanocytes in regenerative medicine applications and disease modeling.Journal of translational medicine · 2024Review
- Functional analysis of recurrent CDC20 promoter variants in human melanoma.Communications biology · 2023Article
- Salvage of ribose from uridine or RNA supports glycolysis in nutrient-limited conditions.Nature metabolism · 2023Article
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- The MITF regulatory network in melanoma.Pigment cell & melanoma research · 2022Article
- Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage.Development (Cambridge, England) · 2022Article
- CYP27A1-dependent anti-melanoma activity of limonoid natural products targets mitochondrial metabolism.Cell chemical biology · 2021Article
- Long non-coding RNA TINCR suppresses metastatic melanoma dissemination by preventing ATF4 translation.EMBO reports · 2021Article
- Article
- The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?Molecular cancer · 2020Review
- MITF functions as a tumor suppressor in non-small cell lung cancer beyond the canonically oncogenic role.Aging · 2020Article
- Article
- PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation.Developmental cell · 2020Article
- Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution.Molecular cell · 2020Article
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9 authors at 1 institution in 1 country.
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Abstract
Thousands of putative enhancers are characterized in the human genome, yet few have been shown to have a functional role in cancer progression. Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by up-regulation of the HGF receptor, MET. The mechanisms mediating such genomic responses to targeted therapy are unknown. Here, we identify lineage-specific enhancers at the MET locus for multiple common tumor types, including a melanoma lineage-specific enhancer 63 kb downstream from the MET TSS. This enhancer displays inducible chromatin looping with the MET promoter to up-regulate MET expression upon BRAF inhibition. Epigenomic analysis demonstrated that the melanocyte-specific transcription factor, MITF, mediates this enhancer function. Targeted genomic deletion (<7 bp) of the MITF motif within the MET enhancer suppressed inducible chromatin looping and innate drug resistance, while maintaining MITF-dependent, inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus guide functional disruption of regulatory DNA to decouple pro- and anti-oncogenic functions of a dominant transcription factor and block innate resistance to oncokinase therapy.
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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.