mda-9/syntenin:: A positive regulator of melanoma metastasis (Publication with Expression of Concern. See vol. 79, pg. 5127, 2019)

被引:96
作者
Boukerche, H
Su, ZZ
Emdad, L
Baril, P
Balme, B
Thomas, L
Randolph, A
Valerie, K
Sarkar, D
Fisher, PB
机构
[1] Columbia Univ, Med Ctr, Dept Pathol, Coll Phys & Surg,Herbert Irving Comprehens Canc C, New York, NY 10032 USA
[2] Columbia Univ, Med Ctr, Dept Urol, Coll Phys & Surg,Herbert Irving Comprehens Canc C, New York, NY 10032 USA
[3] Columbia Univ, Med Ctr, Dept Neurosurg, Coll Phys & Surg,Herbert Irving Comprehens Canc C, New York, NY 10032 USA
[4] Hop Hotel Dieu, Dept Pathol, F-69288 Lyon, France
[5] Hop Hotel Dieu, Dept Dermatol, F-69288 Lyon, France
[6] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA
[7] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA
关键词
D O I
10.1158/0008-5472.CAN-05-1614
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastasis is a significant event in cancer progression and continues to pose the greatest challenge for a cancer cure. Defining genes that control metastasis in vivo may provide new targets for intervening in this process with profound therapeutic implications. Melanoma differentiation associated gene-9 (mda-9) was initially identified by subtraction hybridization as a novel gene displaying biphasic expression during terminal differentiation in human melanoma cells. Mda-9, also known as syntenin, is a PDZ-domain protein overexpressed in many types of human cancers, where it is believed to function in tumor progression. However, a functional role of mda-9/ syntenin in tumor growth and metastasis and the signaling pathways involved in mediating these biological activities remain to be defined. Evidence is now provided, using weakly and highly metastatic isogenic melanoma variants, that mda-9/ syntenin regulates metastasis. Expression of mda-9/syntenin correlates with advanced stages of melanoma progression. Regulating mda-9/syntenin expression using a replication-incompetent adenovirus expressing either sense or antisense mda-9/syntenin modifies the transformed phenotype and alters metastatic ability in immortal human melanocytes and metastatic melanoma cells in vitro and in vivo in newborn rats. A direct relationship is observed between mda-9/syntenin expression and increased phosphorylation of focal adhesion kinase, c-Jun-NH2-kinase, and p38. This study provides the first direct link between mda-9/syntenin expression and tumor cell dissemination in vivo and indicates that mda-9/syntenin expression activates specific signal transduction pathways, which may regulate melanoma tumor progression. Based on its ability to directly alter metastasis, mda-9/syntenin provides a promising new focus for melanoma cancer research with potential therapeutic applications for metastatic diseases.
引用
收藏
页码:10901 / 10911
页数:11
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