期刊
CANCER SCIENCE
卷 110, 期 5, 页码 1525-1535出版社
WILEY
DOI: 10.1111/cas.13999
关键词
cancer; oncogene; Ras; Raf; ERK; Sprouty; Spred; tumor suppressor
类别
资金
- Japan Agency for Medical Research and Development [JP18gm6210008, JP19gm6210008]
- Japan Society for the Promotion of Science [JP15K21775]
- Kibou Projects Startup Support for Young Researchers in Immunology
- Astellas Foundation for Research on Metabolic Disorders
- SENSHIN Medical Research Foundation
- Bristol-Myers Squibb
- SGH Foundation
- MSD Life Science Foundation
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Yasuda Medical Foundation
- Suzuken Memorial Foundation
- Pancreas Research Foundation of Japan
- Waksman Foundation of Japan Inc.
- Japanese Foundation for Multidisciplinary Treatment of Cancer
- Japan Cancer Society
- Okinaka Memorial Institute for Medical Research
- Asahi Glass Foundation
- Foundation for Promotion of Cancer Research
- Kobayashi Foundation for Cancer Research
- Toray Science Foundation
- Vehicle Racing Commemorative Foundation
- JSR-Keio University Medical and Chemical Innovation Center (JKiC)
- Princess Takamatsu Cancer Research Fund
- Tokyo Biomedical Research Foundation
- Daiichi Sankyo Foundation of Life Science
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Japan Medical Association
- Terumo Foundation for Life Sciences and Arts
- Life Science Foundation of Japan
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Yakult-Bioscience Foundation
- Takeda Science Foundation
The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.
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