University of Texas Health Science Center at Houston
Methylation of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling and Cetuximab Resistance
Abstract
dc:description.abstract<p>Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment and poorer overall survival in colorectal cancer patients. These data suggest that R198/R200 methylation plays important role in regulating EGFR functionality and resistance to cetuximab treatment.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2015
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Liao, Hsin-Wei
- Contributors dc:contributor
-
- Mien-Chie Hung, Ph.D
- Dihua Yu, M.D., Ph.D.
- Hui-Kuan Lin, Ph.D.
Subjects
dc:subject × 8Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/615
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1652