Kashyap, A. and Zimmerman, T. and Erguel, N. and Bosserhoff, A. and Hartman, U. and Alla, V. and Bataille, F. and Galle, P. R. and Strand, S. and Strand, D. (2013) The human Lgl polarity gene, Hugl-2, induces MET and suppresses Snail tumorigenesis. ONCOGENE, 32 (11). pp. 1396-1407. ISSN 0950-9232, 1476-5594
Full text not available from this repository. (Request a copy)Abstract
Lethal giant larvae proteins have key roles in regulating polarity in a variety of cell types and function as tumour suppressors. A transcriptional programme initiated by aberrant Snail expression transforms epithelial cells to potentially aggressive cancer cells. Although progress in defining the molecular determinants of this programme has been made, we have little knowledge as to how the Snail-induced phenotype can be suppressed. In our studies we identified the human lethal giant larvae homologue 2, Hugl-2, (Llgl2/Lgl2) polarity gene as downregulated by Snail. Snail binds E-boxes in the Hugl-2 promoter and represses Hugl-2 expression, whereas removal of the E-boxes releases Hugl-2 from Snail repression. We demonstrate that inducing Hugl-2 in cells with constitutive Snail expression reverses the phenotype including changes in morphology, motility, tumour growth and dissemination in vivo, and expression of epithelial markers. Hugl-2 expression reduced the nuclear localization of Snail and thus binding of Snail to its target promoters. Our results placing Hugl-2 within the Snail network as well as its ability to suppress Snail carcinogenesis identifies Hugl-2 as a target molecule driving cascades, which may have preventative and therapeutic promise to minimize cancer progression. Oncogene (2013) 32, 1396-1407; doi:10.1038/onc.2012.162; published online 14 May 2012
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTION FACTOR SNAIL; SQUAMOUS-CELL CARCINOMAS; E-CADHERIN EXPRESSION; TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; DROSOPHILA-MELANOGASTER; PANCREATIC-CANCER; BREAST-CANCER; PRIMARY HEAD; Lgl; Hugl-2; Snail; EMT; MET; tumour suppression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2020 06:01 |
| Last Modified: | 23 Apr 2020 06:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16981 |
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