title: Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer.
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.
authors.affiliation: First Department of Internal Medicine, Johannes Gutenberg University, 55101 Mainz, Germany.
authors.forename: Carl C
authors.initials: CC
authors.lastname: Schimanski
authors.forename: Gösta
authors.initials: G
authors.lastname: Schmitz
authors.forename: Anuba
authors.initials: A
authors.lastname: Kashyap
authors.forename: Anja K
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schäfer
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Susanne
authors.initials: S
authors.lastname: Strand
authors.forename: Dennis
authors.initials: D
authors.lastname: Strand
mesh_terms: D000236:Adenoma / Q000378:metabolism; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002277:Carcinoma / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C097906:LLGL1 protein, human; D011506:Proteins; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; D049452:Green Fluorescent Proteins