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Review
. 2019 May;110(5):1525-1535.
doi: 10.1111/cas.13999. Epub 2019 Apr 23.

The Sprouty/Spred family as tumor suppressors: Coming of age

Tetsuro Kawazoe  1   2 , Koji Taniguchi  1
Affiliations
Review

The Sprouty/Spred family as tumor suppressors: Coming of age

Tetsuro Kawazoe et al. Cancer Sci. 2019 May.

Abstract

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.

Keywords: Ras/Raf/ERK; Sprouty/Spred; cancer; oncogene; tumor suppressor.

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Figures

Figure 1
Figure 1
Inhibitory mechanisms of Sproutys on the Ras/Raf/ERK pathway. DUSP, dual‐specificity phosphatase; miR‐21, microRNA‐21; SHP‐2, Src homology 2 domain‐containing protein tyrosine phosphatase‐2; SOS, Son of Sevenless
Figure 2
Figure 2
Inhibitory mechanisms of Spreds on the Ras/Raf/ERK pathway. DUSP, dual‐specificity phosphatase; miR‐126, microRNA‐126; SHP‐2, Src homology 2 domain‐containing protein tyrosine phosphatase‐2; SOS, Son of Sevenless
See this image and copyright information in PMC

References

    1. Mason JM, Morrison DJ, Basson MA, Licht JD. Sprouty proteins: multifaceted negative‐feedback regulators of receptor tyrosine kinase signaling. Trends Cell Biol. 2006;16:45‐54. - PubMed
    1. Masoumi‐Moghaddam S, Amini A, Morris DL. The developing story of Sprouty and cancer. Cancer Metastasis Rev. 2014;33:695‐720. - PMC - PubMed
    1. Bundschu K, Walter U, Schuh K. Getting a first clue about SPRED functions. BioEssays. 2007;29:897‐907. - PubMed
    1. Yoshimura A. Regulation of cytokine signaling by the SOCS and Spred family proteins. Keio J Med. 2009;58:73‐83. - PubMed
    1. Brems H, Chmara M, Sahbatou M, et al. Germline loss‐of‐function mutations in SPRED1 cause a neurofibromatosis 1‐like phenotype. Nat Genet. 2007;39:1120‐1126. - PubMed

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