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

Details

Serval ID
serval:BIB_8C1EAECC6C46
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer
Journal
Oncogene
Author(s)
Schimanski  C. C., Schmitz  G., Kashyap  A., Bosserhoff  A. K., Bataille  F., Schafer  S. C., Lehr  H. A., Berger  M. R., Galle  P. R., Strand  S., Strand  D.
ISSN
0950-9232 (Print)
Publication state
Published
Issued date
2005
Volume
24
Number
19
Pages
3100-3109
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
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
Keywords
Adenoma/metabolism/Adult/Animals/Blotting,Western/Caco-2 Cells/Carcinoma/Cell Adhesion/Cell Cycle/Cell Differentiation/Cell Line/Cell Line,Tumor/Cell Movement/Colorectal Neoplasms/Cytoskeletal Proteins/Cytoskeleton/Disease Progression/Down-Regulation/Drosophila Proteins/Drosophila melanogaster/Female/Gene Expression Regulation,Neoplastic/Green Fluorescent Proteins/Humans/Immunohistochemistry/Intestinal Mucosa/Male/Microscopy,Fluorescence/Middle Aged/Neoplasms/Protein Structure,Tertiary/Proteins/genetics/Reverse Transcriptase Polymerase Chain Reaction/Transcription,Genetic/Tumor Suppressor Proteins
Pubmed
Web of science
Create date
29/01/2008 18:33
Last modification date
20/08/2019 14:50
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