Journal
CANCER CELL
Volume 24, Issue 4, Pages 512-527Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2013.08.023
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Funding
- FORUN program of Rostock University Medical Center
- German Federal Ministry of Education and Research as part of the project eBio:SysMet [0316171]
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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 IGF1 R regulation as major activity of DNp73.
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