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01-10-2012 | Viewpoint

New insights into signalling networks regulating breast cancer stem cells

Authors: Alexander Swarbrick, Roger J Daly

Published in: Breast Cancer Research | Issue 5/2012

Abstract

In a recent paper, Aceto and colleagues report that Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp2) plays a critical role in maintenance of breast tumour-initiating cells, and they define novel effectors downstream of Shp2 that regulate cellular invasion and self-renewal, including the transcription factors c-Myc and zinc finger E-box binding homeobox 1 and the suppressor of miRNA biogenesis lin-28 homolog B. These findings provide important mechanistic insights into breast tumourigenesis and highlight Shp2 as a potential therapeutic target.

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Aceto N, Sausgruber N, Brinkhaus H, Gaidatzis D, Martiny-Baron G, Mazzarol G, Confalonieri S, Quarto M, Hu G, Balwierz PJ, Pachkov M, Elledge SJ, van Nimwegen E, Stadler MB, Bentires-Alj M: Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop. Nat Med. 2012, 18: 529-537. 10.1038/nm.2645.CrossRefPubMed

Wohrle FU, Daly RJ, Brummer T: Function, regulation and pathological roles of the Gab/DOS docking proteins. Cell Commun Signal. 2009, 7: 22-10.1186/1478-811X-7-22.CrossRefPubMedPubMedCentral

Grossmann KS, Rosario M, Birchmeier C, Birchmeier W: The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res. 2010, 106: 53-89.CrossRefPubMed

Daly RJ, Gu H, Parmar J, Malaney S, Lyons RJ, Kairouz R, Head DR, Henshall SM, Neel BG, Sutherland RL: The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer. Oncogene. 2002, 21: 5175-5181. 10.1038/sj.onc.1205522.CrossRefPubMed

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Bocanegra M, Bergamaschi A, Kim YH, Miller MA, Rajput AB, Kao J, Langerod A, Han W, Noh DY, Jeffrey SS, Huntsman DG, Borresen-Dale AL, Pollack JR: Focal amplification and oncogene dependency of GAB2 in breast cancer. Oncogene. 2010, 29: 774-779. 10.1038/onc.2009.364.CrossRefPubMed

Fleuren ED, O'Toole S, Millar EK, McNeil C, Lopez-Knowles E, Boulghourjian A, Croucher DR, Schramek D, Brummer T, Penninger JM, Sutherland RL, Daly RJ: Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development. Int J Cancer. 2010, 127: 1486-1492. 10.1002/ijc.25172.CrossRefPubMed

Zhou XD, Agazie YM: Inhibition of SHP2 leads to mesenchymal to epithelial transition in breast cancer cells. Cell Death Differ. 2008, 15: 988-996. 10.1038/cdd.2008.54.CrossRefPubMed

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Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ: A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008, 68: 7846-7854. 10.1158/0008-5472.CAN-08-1942.CrossRefPubMed

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13.

Hellmuth K, Grosskopf S, Lum CT, Wurtele M, Roder N, von Kries JP, Rosario M, Rademann J, Birchmeier W: Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking. Proc Natl Acad Sci USA. 2008, 105: 7275-7280. 10.1073/pnas.0710468105.CrossRefPubMedPubMedCentral

Title: New insights into signalling networks regulating breast cancer stem cells
Authors: Alexander Swarbrick
Roger J Daly
Publication date: 01-10-2012
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 5/2012
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr3209

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