Abstract：
:Most squamous cell carcinomas of the head and neck (HNSCC) overexpress ERBB1/EGFR, but EGF receptor (EGFR)-targeted therapies have yielded disappointing clinical results in treatment of this cancer. Here, we describe a novel interaction between EGFR and the ligand EphrinB1 (EFNB1), and we show that EFNB1 phosphorylation and downstream signaling persists in the presence of cetuximab. Mechanistically, cetuximab drives a shift in EGFR dimerization partners within the signaling complex, suggesting that targeted drugs may trigger partner rearrangements that allow persistent pathway activation. EFNB1 attenuation slowed tumor growth and increased survival in a murine model of HNSCC, suggesting a substantial contribution of EFNB1 signaling to HNSCC development. Together, our findings suggest that EFNB1 is part of the EGFR signaling complex and may mediate drug resistance in HNSCC as well as other solid tumors.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Vermeer PD,Colbert PL,Wieking BG,Vermeer DW,Lee JHdoi
10.1158/0008-5472.CAN-13-0760subject
Has Abstractpub_date
2013-09-15 00:00:00pages
5787-97issue
18eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-0760journal_volume
73pub_type
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