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- Title
LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma.
- Authors
Dormoy, V; Béraud, C; Lindner, V; Thomas, L; Coquard, C; Barthelmebs, M; Jacqmin, D; Lang, H; Massfelder, T
- Abstract
Human clear cell renal cell carcinoma (CCC) remains resistant to therapies. The transcription factor LIM-class homeobox gene Lim1 is required for normal organogenesis, including nephrogenesis, by regulating cell movements, differentiation and growth. Its expression is controlled partly by the sonic hedgehog-Gli signaling pathway, which we have recently shown to be reactivated in human CCC. So far, no study has assessed whether Lim1 may be associated with tumorigenesis. Using a panel of human CCC cell lines expressing or not the von Hippel-Lindau tumor suppressor gene and 44 tumor/normal tissues pairs, we found that Lim1 is constitutively and exclusively reexpressed in tumors. Through Lim1 silencing or overexpressing, we show that Lim1 is a growth and survival factor in human CCC, at least through the activation of oncogenic pathways including the phosphoinositide kinase-3/Akt and nuclear factor-kappaB pathways. More importantly, in nude mice bearing human CCC tumors, Lim1 silencing abolished tumor growth through the same mechanism as in vitro. In Lim1-depleted cells and tumors, cell movements were substantially impaired because of the inhibition of expression of various proteins involved in metastatic spread, such as paxillin or tenascin-C. These findings establish that the developmental marker Lim1 acts as an oncogene in cancer cells and targeting Lim1 may constitute an innovative therapeutic intervention in human CCC.
- Subjects
HOMEOBOX genes; ONCOGENES; RENAL cell carcinoma; TRANSCRIPTION factors; GENETIC regulation; GENE expression; CANCER treatment; GENE therapy; CANCER cells; CARCINOGENESIS; GENE silencing
- Publication
Oncogene, 2011, Vol 30, Issue 15, p1753
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.557