“Our study investigated the role of extracellular methylation in EGFR signaling, and unexpectedly discovered new information about how EGFR renders cancer cells resistant to cetuximab antibody therapy,” said Mien Chie Hung, Ph.D., chair of Molecular and Cellular Oncology.
Methylation is a process by which proteins are chemically altered. EGFR, when expressed aberrantly, can lead to cellular changes including runaway cell growth, reduced cell death, tumor formation and metastasis. Hung’s group found that expression of methylation-defective EGFR reduced tumor growth in mice.
“More importantly, we showed that increased methylation of EGFR resulted in resistance to cetuximab mediated cancer cell growth,” said Hung. “This correlated with poorer clinical outcomes in colorectal cancer patients and higher recurrence rates following cetuximab treatment.”
The study showed EGFR methylation was mediated by PRMT1, a protein involved in a variety of genetic processes including gene transcription, DNA repair and signaling.
“EGFR methylation sustained signaling activity and cell proliferation even in the presence of cetuximab,” said Hung. “This data suggests that this specific methylation plays an important role in regulating EGFR functionality and resistance to cetuximab treatment.”