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RESEARCH PRODUCT
Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer.
Peter R. GalleDennis StrandAnuba KashyapAnja K. BosserhoffHans A. LehrSusanne StrandGösta SchmitzMartin R. BergerFrauke BatailleStephan C. SchäferCarl C. Schimanskisubject
MaleCancer ResearchTranscription Geneticmedicine.disease_causeCell MovementNeoplasmsGene expressionDrosophila ProteinsIntestinal MucosaCytoskeletonReverse Transcriptase Polymerase Chain ReactionCell CycleCell migrationCell DifferentiationMiddle AgedImmunohistochemistryGene Expression Regulation NeoplasticDrosophila melanogasterDisease ProgressionFemaleColorectal NeoplasmsAdenomaAdultTumor suppressor geneBlotting WesternGreen Fluorescent ProteinsDown-RegulationBiologyCell LineDownregulation and upregulationCell Line TumorGeneticsmedicineCell AdhesionAnimalsHumansCell adhesionMolecular BiologyGeneTumor Suppressor ProteinsCarcinomaProteinsProtein Structure TertiaryCytoskeletal ProteinsMicroscopy FluorescenceTumor progressionImmunologyCancer researchCaco-2 CellsCarcinogenesisdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-03-01 | Oncogene |