Title |
A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer
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Published in |
Cell Reports, October 2017
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DOI | 10.1016/j.celrep.2017.10.015 |
Pubmed ID | |
Authors |
Paul Savage, Alexis Blanchet-Cohen, Timothée Revil, Dunarel Badescu, Sadiq M.I. Saleh, Yu-Chang Wang, Dongmei Zuo, Leah Liu, Nicholas R. Bertos, Valentina Munoz-Ramos, Mark Basik, Kevin Petrecca, Jamil Asselah, Sarkis Meterissian, Marie-Christine Guiot, Atilla Omeroglu, Claudia L. Kleinman, Morag Park, Jiannis Ragoussis |
Abstract |
Therapies targeting epidermal growth factor receptor (EGFR) have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster. Sorted EGFR(hi) subpopulations exhibited enhanced stem-like features, including ALDH activity, sphere-forming efficiency, and tumorigenic and metastatic potential. EGFR(hi) cells gave rise to EGFR(hi) and EGFR(lo) cells in primary and metastatic tumors, demonstrating an EGFR-dependent expansion and hierarchical state transition. Similar tumorigenic EGFR(hi) subpopulations were identified in independent PDXs, where heterogeneous EGFR expression correlated with gefitinib sensitivity. This provides new understanding for an EGFR-dependent hierarchy in TNBC and for patient stratification for therapeutic intervention. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 9 | 21% |
United States | 6 | 14% |
United Kingdom | 3 | 7% |
Germany | 2 | 5% |
Belgium | 1 | 2% |
Spain | 1 | 2% |
Portugal | 1 | 2% |
Turkey | 1 | 2% |
Austria | 1 | 2% |
Other | 5 | 12% |
Unknown | 13 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 22 | 51% |
Members of the public | 17 | 40% |
Science communicators (journalists, bloggers, editors) | 3 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 173 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 37 | 21% |
Researcher | 28 | 16% |
Student > Master | 16 | 9% |
Student > Bachelor | 15 | 9% |
Student > Doctoral Student | 10 | 6% |
Other | 28 | 16% |
Unknown | 39 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 56 | 32% |
Agricultural and Biological Sciences | 30 | 17% |
Medicine and Dentistry | 12 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 5% |
Immunology and Microbiology | 4 | 2% |
Other | 18 | 10% |
Unknown | 44 | 25% |