| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 3975 |
Name | LHX1 |
Synonymous | LIM homeobox 1;LHX1;LIM homeobox 1 |
Definition | LIM homeobox protein 1|LIM/homeobox protein Lhx1|homeobox protein Lim-1 |
Position | 17q12 |
Gene type | protein-coding |
Title | Abstract |
| LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma. | 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. |