Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer

Oncogene. 2005 Apr 28;24(19):3100-9. doi: 10.1038/sj.onc.1208520.


The human gene, human giant larvae (Hugl-1/Llg1/Lgl1) has significant homology to the Drosophila tumour suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that binds Myosin II and is involved in maintaining cell polarity and epithelial integrity. The human protein, Hugl-1 contains several conserved functional domains found in Lgl, suggesting that these proteins may have closely related functions. Whether loss of Hugl expression plays a role in human tumorigenesis has so far not been extensively investigated. Thus, we evaluated tumour tissues from 94 patients undergoing surgery for colorectal cancer (CRC) for loss of Hugl-1 transcription and compared our findings with the clinical data from each of these patients. We found that Hugl-1 was lost in 75% of tumour samples and these losses were associated with advanced stage and particularly with lymph node metastases. Reduced Hugl-1 expression during the adenoma-carcinoma sequence occurring as early as in colorectal adenomas was detected by both immunohistochemical and reverse transcription-polymerase chain reaction analysis. Functional assays with ecdysone-inducible cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Our studies thus indicate that downregulation of Hugl-1 contributes to CRC progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism
  • Adult
  • Animals
  • Blotting, Western
  • Caco-2 Cells
  • Carcinoma / metabolism
  • Cell Adhesion
  • Cell Cycle
  • Cell Differentiation
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / metabolism*
  • Cytoskeletal Proteins
  • Cytoskeleton / metabolism
  • Disease Progression
  • Down-Regulation
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Neoplasms / metabolism
  • Protein Structure, Tertiary
  • Proteins / genetics
  • Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Tumor Suppressor Proteins / metabolism


  • Cytoskeletal Proteins
  • Drosophila Proteins
  • LLGL1 protein, human
  • Proteins
  • Tumor Suppressor Proteins
  • l(2)gl protein, Drosophila
  • Green Fluorescent Proteins