Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Mien-Chie Hung, Ph.D

Committee Member

Dihua Yu, M.D., Ph.D.

Committee Member

Hui-Kuan Lin, Ph.D.

Committee Member

Liuqing Yang, Ph.D.

Committee Member

Pierre D. McCrea, Ph.D.


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.


PRMT1, EGFR, methylation, cetuximab, colorectal cancer



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