Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer

Ying Nai Wang; Heng Huan Lee; Chao Kai Chou; Wen Hao Yang; Yongkun Wei; Chun Te Chen; Jun Yao; Jennifer L. Hsu; Cihui Zhu; Haoqiang Ying; Yuanqing Ye; Wei Jan Wang; Seung Oe Lim; Weiya Xia; How Wen Ko; Xiuping Liu; Chang Gong Liu; Xifeng Wu; Huamin Wang; Donghui Li; Laura R. Prakash; Matthew H. Katz; Yaan Kang; Michael Kim; Jason B. Fleming; David Fogelman; Milind Javle; Anirban Maitra; Mien Chie Hung

doi:10.1016/j.ccell.2018.02.012

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer

Ying Nai Wang, Heng Huan Lee, Chao Kai Chou, Wen Hao Yang, Yongkun Wei, Chun Te Chen, Jun Yao, Jennifer L. Hsu, Cihui Zhu, Haoqiang Ying, Yuanqing Ye, Wei Jan Wang, Seung Oe Lim, Weiya Xia, How Wen Ko, Xiuping Liu, Chang Gong Liu, Xifeng Wu, Huamin Wang, Donghui LiLaura R. Prakash, Matthew H. Katz, Yaan Kang, Michael Kim, Jason B. Fleming, David Fogelman, Milind Javle, Anirban Maitra, Mien Chie Hung

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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. Wang et al. identify angiogenin (ANG) as a ligand for epidermal growth factor receptor (EGFR). ANG-mediated EGFR activation can trigger oncogenic transformation, and high ANG in the plasma of pancreatic adenocarcinoma patients positively correlates with response to the EGFR inhibitor erlotinib.

Original language	English (US)
Pages (from-to)	752-769.e8
Journal	Cancer Cell
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2018.02.012
State	Published - Apr 9 2018
Externally published	Yes

Keywords

EGFR inhibitor
EGFR ligand
PDAC
angiogenin
erlotinib
receptor tyrosine kinase
ribonuclease
serum biomarker

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2018.02.012

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Wang, Y. N., Lee, H. H., Chou, C. K., Yang, W. H., Wei, Y., Chen, C. T., Yao, J., Hsu, J. L., Zhu, C., Ying, H., Ye, Y., Wang, W. J., Lim, S. O., Xia, W., Ko, H. W., Liu, X., Liu, C. G., Wu, X., Wang, H., ... Hung, M. C. (2018). Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer. Cancer Cell, 33(4), 752-769.e8. https://doi.org/10.1016/j.ccell.2018.02.012

Wang, YN, Lee, HH, Chou, CK, Yang, WH, Wei, Y, Chen, CT, Yao, J, Hsu, JL, Zhu, C, Ying, H, Ye, Y, Wang, WJ, Lim, SO, Xia, W, Ko, HW, Liu, X, Liu, CG, Wu, X, Wang, H, Li, D, Prakash, LR, Katz, MH, Kang, Y, Kim, M, Fleming, JB, Fogelman, D, Javle, M, Maitra, A & Hung, MC 2018, 'Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer', Cancer Cell, vol. 33, no. 4, pp. 752-769.e8. https://doi.org/10.1016/j.ccell.2018.02.012

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title = "Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer",

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. Wang et al. identify angiogenin (ANG) as a ligand for epidermal growth factor receptor (EGFR). ANG-mediated EGFR activation can trigger oncogenic transformation, and high ANG in the plasma of pancreatic adenocarcinoma patients positively correlates with response to the EGFR inhibitor erlotinib.",

keywords = "EGFR inhibitor, EGFR ligand, PDAC, angiogenin, erlotinib, receptor tyrosine kinase, ribonuclease, serum biomarker",

author = "Wang, {Ying Nai} and Lee, {Heng Huan} and Chou, {Chao Kai} and Yang, {Wen Hao} and Yongkun Wei and Chen, {Chun Te} and Jun Yao and Hsu, {Jennifer L.} and Cihui Zhu and Haoqiang Ying and Yuanqing Ye and Wang, {Wei Jan} and Lim, {Seung Oe} and Weiya Xia and Ko, {How Wen} and Xiuping Liu and Liu, {Chang Gong} and Xifeng Wu and Huamin Wang and Donghui Li and Prakash, {Laura R.} and Katz, {Matthew H.} and Yaan Kang and Michael Kim and Fleming, {Jason B.} and David Fogelman and Milind Javle and Anirban Maitra and Hung, {Mien Chie}",

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doi = "10.1016/j.ccell.2018.02.012",

language = "English (US)",

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AU - Wang, Ying Nai

AU - Lee, Heng Huan

AU - Chou, Chao Kai

AU - Yang, Wen Hao

AU - Wei, Yongkun

AU - Chen, Chun Te

AU - Yao, Jun

AU - Hsu, Jennifer L.

AU - Zhu, Cihui

AU - Ying, Haoqiang

AU - Ye, Yuanqing

AU - Wang, Wei Jan

AU - Lim, Seung Oe

AU - Xia, Weiya

AU - Ko, How Wen

AU - Liu, Xiuping

AU - Liu, Chang Gong

AU - Wu, Xifeng

AU - Wang, Huamin

AU - Li, Donghui

AU - Prakash, Laura R.

AU - Katz, Matthew H.

AU - Kang, Yaan

AU - Kim, Michael

AU - Fleming, Jason B.

AU - Fogelman, David

AU - Javle, Milind

AU - Maitra, Anirban

AU - Hung, Mien Chie

PY - 2018/4/9

Y1 - 2018/4/9

N2 - 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. Wang et al. identify angiogenin (ANG) as a ligand for epidermal growth factor receptor (EGFR). ANG-mediated EGFR activation can trigger oncogenic transformation, and high ANG in the plasma of pancreatic adenocarcinoma patients positively correlates with response to the EGFR inhibitor erlotinib.

AB - 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. Wang et al. identify angiogenin (ANG) as a ligand for epidermal growth factor receptor (EGFR). ANG-mediated EGFR activation can trigger oncogenic transformation, and high ANG in the plasma of pancreatic adenocarcinoma patients positively correlates with response to the EGFR inhibitor erlotinib.

KW - EGFR inhibitor

KW - EGFR ligand

KW - PDAC

KW - angiogenin

KW - erlotinib

KW - receptor tyrosine kinase

KW - ribonuclease

KW - serum biomarker

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SN - 1535-6108

VL - 33

SP - 752-769.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer

Abstract

Keywords

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