Journal
CANCER CELL
Volume 33, Issue 4, Pages 752-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.02.012
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Funding
- NIH [CCSG CA016672, RO1 CA211615, U01 CA201777]
- University of Texas MD Anderson-China Medical University
- Hospital Sister Institution Fund
- Breast Cancer Research Foundation [BCRF-17-069]
- Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence [MOHW106-TDU-B-212-144003]
- T32 Training Grant in Cancer Biology [5T32CA186892]
- Center for Biological Pathways
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Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin [ANG]) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a role of ANG as a serum biomarker that may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.
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