LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma

Oncogene. 2011 Apr 14;30(15):1753-63. doi: 10.1038/onc.2010.557. Epub 2010 Dec 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Proliferation
  • Gene Silencing
  • Homeodomain Proteins / genetics*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • LIM-Homeodomain Proteins
  • Mice
  • Mice, Nude
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcription Factors


  • Homeodomain Proteins
  • LHX1 protein, human
  • LIM-Homeodomain Proteins
  • Transcription Factors