Nature Communications (Aug 2018)
SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling
- Thomas Strub,
- Flavia G. Ghiraldini,
- Saul Carcamo,
- Man Li,
- Aleksandra Wroblewska,
- Rajendra Singh,
- Matthew S. Goldberg,
- Dan Hasson,
- Zichen Wang,
- Stuart J. Gallagher,
- Peter Hersey,
- Avi Ma’ayan,
- Georgina V. Long,
- Richard A. Scolyer,
- Brian Brown,
- Bin Zheng,
- Emily Bernstein
Affiliations
- Thomas Strub
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- Flavia G. Ghiraldini
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- Saul Carcamo
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- Man Li
- Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School
- Aleksandra Wroblewska
- Department of Genetics and Genomic Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai
- Rajendra Singh
- Department of Dermatology, Icahn School of Medicine at Mount Sinai
- Matthew S. Goldberg
- Department of Dermatology, Icahn School of Medicine at Mount Sinai
- Dan Hasson
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- Zichen Wang
- Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai
- Stuart J. Gallagher
- Centenary Institute, Camperdown NSW 2050, The University of Sydney
- Peter Hersey
- Centenary Institute, Camperdown NSW 2050, The University of Sydney
- Avi Ma’ayan
- Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai
- Georgina V. Long
- Melanoma Institute Australia, Wollstonecraft NSW 2065, The University of Sydney
- Richard A. Scolyer
- Melanoma Institute Australia, Wollstonecraft NSW 2065, The University of Sydney
- Brian Brown
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai
- Bin Zheng
- Centenary Institute, Camperdown NSW 2050, The University of Sydney
- Emily Bernstein
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- DOI
- https://doi.org/10.1038/s41467-018-05966-z
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 13
Abstract
The epigenetic mechanisms of melanoma drug resistance are poorly understood. Here, the authors develop a CRISPR-Cas9 screen targeting epigenetic regulators and discover that SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling.
