| Literature DB >> 29606349 |
Ying-Nai Wang1, Heng-Huan Lee2, Chao-Kai Chou1, Wen-Hao Yang2, Yongkun Wei2, Chun-Te Chen2, Jun Yao2, Jennifer L Hsu1, Cihui Zhu2, Haoqiang Ying3, Yuanqing Ye4, Wei-Jan Wang2, Seung-Oe Lim2, Weiya Xia2, How-Wen Ko2, Xiuping Liu5, Chang-Gong Liu5, Xifeng Wu6, Huamin Wang7, Donghui Li8, Laura R Prakash9, Matthew H Katz9, Yaan Kang9, Michael Kim9, Jason B Fleming9, David Fogelman10, Milind Javle10, Anirban Maitra11, Mien-Chie Hung12.
Abstract
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.Entities:
Keywords: EGFR inhibitor; EGFR ligand; PDAC; angiogenin; erlotinib; receptor tyrosine kinase; ribonuclease; serum biomarker
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Year: 2018 PMID： 29606349 PMCID： PMC5893359 DOI： 10.1016/j.ccell.2018.02.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743