The Developing Story of Sprouty and Cancer

Overview

Journal Cancer Metastasis Rev

Specialty Oncology

Date 2014 Apr 19

PMID 24744103

Citations 82

Authors

Samar Masoumi-Moghaddam

Afshin Amini

David Lawson Morris

Affiliations

Soon will be listed here.

Abstract

Sprouty proteins are evolutionarily conserved modulators of MAPK/ERK pathway. Through interacting with an increasing number of effectors, mediators, and regulators with ultimate influence on multiple targets within or beyond ERK, Sprouty orchestrates a complex, multilayered regulatory system and mediates a crosstalk among different signaling pathways for a coordinated cellular response. As such, Sprouty has been implicated in various developmental and physiological processes. Evidence shows that ERK is aberrantly activated in malignant conditions. Accordingly, Sprouty deregulation has been reported in different cancer types and shown to impact cancer development, progression, and metastasis. In this article, we have tried to provide an overview of the current knowledge about the Sprouty physiology and its regulatory functions in health, as well as an updated review of the Sprouty status in cancer. Putative implications of Sprouty in cancer biology, their clinical relevance, and their proposed applications are also revisited. As a developing story, however, role of Sprouty in cancer remains to be further elucidated.

Citing Articles

Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma.

Montico B, Giurato G, Guerrieri R, Colizzi F, Salvati A, Nassa G J Exp Clin Cancer Res. 2025; 44(1):53.

PMID: 39953610 PMC: 11827140. DOI: 10.1186/s13046-025-03289-8.

Three-Dimensional Models: Biomimetic Tools That Recapitulate Breast Tissue Architecture and Microenvironment to Study Ductal Carcinoma In Situ Transition to Invasive Ductal Breast Cancer.

Shah S, Osuala K, Brock E, Ji K, Sloane B, Mattingly R Cells. 2025; 14(3).

PMID: 39937011 PMC: 11817749. DOI: 10.3390/cells14030220.

Sprouty2 Regulates Endocytosis and Degradation of Fibroblast Growth Factor Receptor 1 in Glioblastoma Cells.

Hausott B, Pircher L, Kind M, Park J, Claus P, Obexer P Cells. 2024; 13(23).

PMID: 39682716 PMC: 11639775. DOI: 10.3390/cells13231967.

Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice.

Altes G, Olomi A, Perramon-Guell A, Hernandez S, Casanovas A, Perez A Sci Rep. 2024; 14(1):19479.

PMID: 39174793 PMC: 11341818. DOI: 10.1038/s41598-024-70529-w.

Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53.

Muniz de Queiroz R, Efe G, Guzman A, Hashimoto N, Kawashima Y, Tanaka T Nat Commun. 2024; 15(1):7132.

PMID: 39164253 PMC: 11336179. DOI: 10.1038/s41467-024-51488-2.

References

Klein O, Lyons D, Balooch G, Marshall G, Basson M, Peterka M . An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors. Development. 2007; 135(2):377-85. PMC: 2555979. DOI: 10.1242/dev.015081. View

Tsavachidou D, Coleman M, Athanasiadis G, Li S, Licht J, Olson M . SPRY2 is an inhibitor of the ras/extracellular signal-regulated kinase pathway in melanocytes and melanoma cells with wild-type BRAF but not with the V599E mutant. Cancer Res. 2004; 64(16):5556-9. DOI: 10.1158/0008-5472.CAN-04-1669. View

Fong C, Chua M, McKie A, Ling S, Mason V, Li R . Sprouty 2, an inhibitor of mitogen-activated protein kinase signaling, is down-regulated in hepatocellular carcinoma. Cancer Res. 2006; 66(4):2048-58. DOI: 10.1158/0008-5472.CAN-05-1072. View

Vanas V, Muhlbacher E, Kral R, Sutterluty-Fall H . Sprouty4 interferes with cell proliferation and migration of breast cancer-derived cell lines. Tumour Biol. 2014; 35(5):4447-56. DOI: 10.1007/s13277-013-1587-0. View

Yigzaw Y, Poppleton H, Sreejayan N, Hassid A, Patel T . Protein-tyrosine phosphatase-1B (PTP1B) mediates the anti-migratory actions of Sprouty. J Biol Chem. 2002; 278(1):284-8. DOI: 10.1074/jbc.M210359200. View

Macia A, Gallel P, Vaquero M, Gou-Fabregas M, Santacana M, Maliszewska A . Sprouty1 is a candidate tumor-suppressor gene in medullary thyroid carcinoma. Oncogene. 2011; 31(35):3961-72. PMC: 3378485. DOI: 10.1038/onc.2011.556. View

Frolov A, Chahwan S, Ochs M, Arnoletti J, Pan Z, Favorova O . Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumors. Mol Cancer Ther. 2003; 2(8):699-709. View

Haimov-Kochman R, Ravhon A, Prus D, Greenfield C, Finci-Yeheskel Z, Goldman-Wohl D . Expression and regulation of Sprouty-2 in the granulosa-lutein cells of the corpus luteum. Mol Hum Reprod. 2005; 11(8):537-42. DOI: 10.1093/molehr/gah203. View

Egan J, Hall A, Yatsula B, Bar-Sagi D . The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins. Proc Natl Acad Sci U S A. 2002; 99(9):6041-6. PMC: 122898. DOI: 10.1073/pnas.052090899. View

10.

Haglund K, Schmidt M, Wong E, Guy G, Dikic I . Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation. EMBO Rep. 2005; 6(7):635-41. PMC: 1369112. DOI: 10.1038/sj.embor.7400453. View

11.

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M . MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456(7224):980-4. DOI: 10.1038/nature07511. View

12.

Sigurdsson V, Ingthorsson S, Hilmarsdottir B, Gustafsdottir S, Franzdottir S, Arason A . Expression and functional role of sprouty-2 in breast morphogenesis. PLoS One. 2013; 8(4):e60798. PMC: 3616012. DOI: 10.1371/journal.pone.0060798. View

13.

Pan Y, Carbe C, Powers A, Feng G, Zhang X . Sprouty2-modulated Kras signaling rescues Shp2 deficiency during lens and lacrimal gland development. Development. 2010; 137(7):1085-93. PMC: 2835324. DOI: 10.1242/dev.042820. View

14.

Haglund K, Sigismund S, Polo S, Szymkiewicz I, Di Fiore P, Dikic I . Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nat Cell Biol. 2003; 5(5):461-6. DOI: 10.1038/ncb983. View

15.

Ding W, Warburton D . Down-regulation of Sprouty2 via p38 MAPK plays a key role in the induction of cellular apoptosis by tumor necrosis factor-alpha. Biochem Biophys Res Commun. 2008; 375(3):460-4. PMC: 2575769. DOI: 10.1016/j.bbrc.2008.08.037. View

16.

Minowada G, Miller Y . Overexpression of Sprouty 2 in mouse lung epithelium inhibits urethane-induced tumorigenesis. Am J Respir Cell Mol Biol. 2008; 40(1):31-7. PMC: 2720112. DOI: 10.1165/rcmb.2008-0147OC. View

17.

Harada N, Miyoshi H, Murai N, Oshima H, Tamai Y, Oshima M . Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res. 2002; 62(7):1971-7. View

18.

Lee S, Schloss D, Jarvis L, Krasnow M, Swain J . Inhibition of angiogenesis by a mouse sprouty protein. J Biol Chem. 2000; 276(6):4128-33. DOI: 10.1074/jbc.M006922200. View

19.

Edwin F, Singh R, Endersby R, Baker S, Patel T . The tumor suppressor PTEN is necessary for human Sprouty 2-mediated inhibition of cell proliferation. J Biol Chem. 2005; 281(8):4816-22. DOI: 10.1074/jbc.M508300200. View

20.

Bren-Mattison Y, Van Putten V, Chan D, Winn R, Geraci M, Nemenoff R . Peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC). Oncogene. 2004; 24(8):1412-22. DOI: 10.1038/sj.onc.1208333. View