Journal
JOURNAL OF BIOMEDICAL SCIENCE
Volume 25, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12929-018-0484-7
Keywords
Ribonuclease; Angiogenin; Ligand; Serum biomarker; Receptor tyrosine kinase; Epidermal growth factor receptor; Tyrosine kinase inhibitor; Cancer; Targeted therapy
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Funding
- National Institutes of Health [CCSG CA016672, RO1 CA211615, U01 CA201777]
- University of Texas MD Anderson-China Medical University and 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 [MOHW107-TDU-B-212-114024, MOWH107-TDU-B-212-112015]
- T32 Training Grant in Cancer Biology [5T32CA186892]
- Center for Biological Pathways
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Pancreatic ribonuclease is known to participate in host defense system against pathogens, such as parasites, bacteria, and virus, which results in innate immune response. Nevertheless, its potential impact to host cells remains unclear. Of interest, several ribonucleases do not act as catalytically competent enzymes, suggesting that ribonucleases may be associated with certain intrinsic functions other than their ribonucleolytic activities. Most recently, human pancreatic ribonuclease 5 (hRNase5; also named angiogenin; hereinafter referred to as hRNase5/ANG), which belongs to the human ribonuclease A superfamily, has been demonstrated to function as a ligand of epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase family. As a newly identified EGFR ligand, hRNase5/ANG associates with EGFR and stimulates EGFR and the downstream signaling in a catalytic-independent manner. Notably, hRNase5/ANG, whose level in sera of pancreatic cancer patients, serves as a non-invasive serum biomarker to stratify patients for predicting the sensitivity to EGFR-targeted therapy. Here, we describe the hRNase5/ANG-EGFR pair as an example to highlight a ligand-receptor relationship between families of ribonucleases and receptor tyrosine kinases, which are thought as two unrelated protein families associated with distinct biological functions. The notion of serum biomarker-guided EGFR-targeted therapies will also be discussed. Furthering our understanding of this novel ligand-receptor interaction will shed new light on the search of ligands for their cognate receptors, especially those orphan receptors without known ligands, and deepen our knowledge of the fundamental research in membrane receptor biology and the translational application toward the development of precision medicine.
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