Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer.
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.
Schimanski
Carl C
CC
First Department of Internal Medicine, Johannes Gutenberg University, 55101 Mainz, Germany.
Schmitz
Gösta
G
Kashyap
Anuba
A
Bosserhoff
Anja K
AK
Bataille
Frauke
F
Schäfer
Stephan C
SC
Lehr
Hans A
HA
Berger
Martin R
MR
Galle
Peter R
PR
Strand
Susanne
S
Strand
Dennis
D
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
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