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Oncogene (2010) 29, 54165426
& 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 http://www.nature.com/onc
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ORIGINAL ARTICLE
Lung cancer cell migration is regulated via repressing growth factor PTN/RPTP b/f signaling by menin
Z-J Feng1, S-B Gao1, Y Wu1, X-F Xu2, X Hua3 and G-H Jin1
1Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China; 2Department of Pathology, Xiamen Second Hospital, Xiamen, Fujian, PR China and 3Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA
Menin encoded by the multiple endocrine neoplasia type 1 (MEN1) gene is associated with chromatin and the nuclear matrix and exerts multiple biological functions including regulation of cell proliferation and adhesion.Men1 mutations increase the likelihood of lung cancer development in mice. Menin expression is reduced in certain human non-small cell lung cancer cells, and reduction of menin is closely correlated with increased lung cancer metastasis to lymph nodes. However, it is poorly understood whether menin affects migration of lung cancer cells. In this study, we show that menin-regulated A549 lung cancer cell migration, which was mediated by growth factor pleiotrophin (PTN) and its cell surface receptor, protein tyrosine phosphatase beta/zeta (RPTP b/f). Ectopic menin expression signicantly repressed PTN transcription, but indirectly inhibited RPTP b/f expression through repressing PTN expression.
Further studies revealed that menin-regulated cell migration through PTN/RPTP b/f, in conjunction with integrin avb3, focal adhesion kinase, phosphatidylinositol 3-kinase and phosphorylated extracellular signal regulated kinase 1/2.These ndings provide mechanistic insights into the molecular basis for menin/PTN-mediated regulation of A549 lung cancer cell migration.
Oncogene (2010) 29, 54165426; doi:http://dx.doi.org/10.1038/onc.2010.282
Web End =10.1038/onc.2010.282 ; published online 19 July 2010
Keywords: lung cancer; migration; Men1; pleiotrophin;
RPTP b/z
Introduction
Menin encoded by the multiple endocrine neoplasia type 1 (MEN1) gene is a nuclear protein, which is mutated in patients with an inherited tumor syndrome, MEN1 (Chandrasekharappa et al., 1997). In endocrine tumors with a germline mutation in one of the MEN1 alleles, the remaining wild-type MEN1 allele is often inactivated because of a somatic mutation (loss of heterozygocity),
indicating MEN1 as a bona de tumor suppressor gene in endocrine tumors (Lemos and Thakker, 2008). As menin does not show an obvious homology to any known protein motifs, it has been challenging to elucidate how menin acts...