期刊
SEMINARS IN CANCER BIOLOGY
卷 85, 期 -, 页码 123-154出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2021.05.010
关键词
MAPK; RAF; MEK; ERK; Cancer
类别
资金
- Melanoma Research Alliance
- American Cancer Society
- Florida Department of Health
The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway that plays a critical role in cell proliferation and survival. Genetic alterations in this pathway are highly prevalent in human cancers and can lead to uncontrolled cell growth and tumor formation. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further enhances its proliferative potential in human cancers.
The RAF-MEK-ERK signaling cascade is a well-characterized MAPK pathway involved in cell proliferation and survival. The three-layered MAPK signaling cascade is initiated upon RTK and RAS activation. Three RAF isoforms ARAF, BRAF and CRAF, and their downstream MEK1/2 and ERK1/2 kinases constitute a coherently orchestrated signaling module that directs a range of physiological functions. Genetic alterations in this pathway are among the most prevalent in human cancers, which consist of numerous hot-spot mutations such as BRAFV600E. Oncogenic mutations in this pathway often override otherwise tightly regulated checkpoints to open the door for uncontrolled cell growth and neoplasia. The crosstalk between the RAF-MEK-ERK axis and other signaling pathways further extends the proliferative potential of this pathway in human cancers. In this review, we summarize the molecular architecture and physiological functions of the RAF-MEK-ERK pathway with emphasis on its dysregulations in human cancers, as well as the efforts made to target the RAF-MEK-ERK module using small molecule inhibitors.
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