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MAPK1E322K mutation increases head and neck squamous cell carcinoma sensitivity to erlotinib through enhanced secretion of amphiregulin.
In this study, we investigated the mechanism of MAPK1E322K-mediated EGFR activation in the context of erlotinib sensitivity. We demonstrated increased AREG secretion in HNSCC cell lines harboring endogenous or exogenous MAPK1E322K compared to wild type MAPK1. We found inhibition or knockdown of MAPK1 with siRNA resulted in reduced secretion of AREG and decreased sensitivity to erlotinib in the setting of MAPK1E322K. MAPK1E322K was associated with increased AREG secretion leading to an autocrine feedback loop involving AREG, EGFR and downstream signaling. Knockdown of AREG in HNSCC cells harboring MAPK1E322K abrogated EGFR ...
Source: Oncotarget - March 25, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

HRAS mutations and resistance to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in head and neck squamous cell carcinoma cells
Conclusion: Activating HRAS mutations can confer erlotinib resistance in an HRAS mutant HNSCC cell line. Head Neck, 2013.
Source: Head and Neck - September 30, 2013 Category: ENT & OMF Authors: J. Hun Hah, Mei Zhao, Curtis R. Pickering, Mitchell J. Frederick, Genevieve A. Andrews, Samar A. Jasser, David R. Fooshee, Zvonimir L. Milas, Chad Galer, Daisuke Sano, William N. William, Edward Kim, John Heymach, Lauren A. Byers, Vali Papadimitrakopoulou Tags: Research Article Source Type: research