Cancer Cell, Volume 24, Issue 4, 512-527, 14 October 2013
DNp73 Exerts Function in Metastasis Initiation by Disconnecting the Inhibitory Role of EPLIN on IGF1R-AKT/STAT3 Signaling
Steder M, Alla V, Meier C, Spitschak A, Pahnke J, Fürst K, Kowtharapu BS, Engelmann D, Petigk J, Egberts F, Schäd-Trcka SG, Gross G, Nettelbeck DM, Niemetz A, Pützer BM.
Dissemination of cancer cells from primary tumors is the key event in metastasis, but specific determinants are widely unknown. Here, we show that DNp73, an inhibitor of the p53 tumor suppressor family, drives migration and invasion of nonmetastatic melanoma cells. Knockdown of endogenous DNp73 reduces this behavior in highly metastatic cell lines. Tumor xenografts expressing DNp73 show a higher ability to invade and metastasize, while growth remains unaffected. DNp73 facilitates an EMT-like phenotype with loss of E-cadherin and Slug upregulation. We provide mechanistic insight toward regulation of LIMA1/EPLIN by p73/DNp73 and demonstrate a direct link between the DNp73-EPLIN axis and IGF1R-AKT/STAT3 activation. These findings establish initiation of the invasion-metastasis cascade via EPLIN-dependent IGF1R regulation as major activity of DNp73.
Contact
Institute of Experimental Gene Therapy and Cancer Research
Core-Facility Viral Vector & Genome-Editing Technologies
Biomedical Research Center
Schillingallee 69
D-18057 Rostock
Office
Ingrid Winkler
(+49) 381 494-5066(+49) 381 494-5062
ingrid.winkler@med.uni-rostock.de
Department Life, Light & Matter
Research Building LL&M
Albert-Einstein-Str. 25
D-18059 Rostock
Research Building LL&M
Albert-Einstein-Str. 25
D-18059 Rostock
