Deregulation of FoxM1b leads to tumour metastasis
| العنوان: | Deregulation of FoxM1b leads to tumour metastasis |
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| المؤلفون: | Yoon Dong Park, Hyun Jung Park, Jin Qiu, Janai R. Carr, Pradip Raychaudhuri, Galina A. Gusarova, Peter R. Williamson, Robert H. Costa, Jing Li, Nissim Hay, Lester F. Lau, Ki-Hyun Kim, Zebin Wang, Angela L. Tyner |
| المصدر: | EMBO Molecular Medicine |
| بيانات النشر: | EMBO, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Liver Cirrhosis, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Mice, Transgenic, Stathmin, Lysyl oxidase, Metastasis, Protein-Lysine 6-Oxidase, Mice, 03 medical and health sciences, 0302 clinical medicine, Conditional gene knockout, medicine, Carcinoma, Animals, Humans, metastasis, Epithelial–mesenchymal transition, Neoplasm Metastasis, Transcription factor, Research Articles, 030304 developmental biology, 0303 health sciences, biology, ADP-Ribosylation Factors, Forkhead Box Protein M1, Liver Neoplasms, Arf, Forkhead Transcription Factors, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, FoxM1, biology.protein, Cancer research, FOXM1, Molecular Medicine, Snail Family Transcription Factors, Proto-Oncogene Proteins c-akt, Signal Transduction, Transcription Factors |
| الوصف: | The forkhead box M1b (FoxM1b) transcription factor is over-expressed in human cancers, and its expression often correlates with poor prognosis. Previously, using conditional knockout strains, we showed that FoxM1b is essential for hepatocellular carcinoma (HCC) development. However, over-expression of FoxM1b had only marginal effects on HCC progression. Here we investigated the effect of FoxM1b expression in the absence of its inhibitor Arf. We show that transgenic expression of FoxM1b in an Arf-null background drives hepatic fibrosis and metastasis of HCC. We identify novel mechanisms of FoxM1b that are involved in epithelial–mesenchymal transition, cell motility, invasion and a pre-metastatic niche formation. FoxM1b activates the Akt-Snail1 pathway and stimulates expression of Stathmin, lysyl oxidase, lysyl oxidase like-2 and several other genes involved in metastasis. Furthermore, we show that an Arf-derived peptide, which inhibits FoxM1b, impedes metastasis of the FoxM1b-expressing HCC cells. The observations indicate that FoxM1b is a potent activator of tumour metastasis and that the Arf-mediated inhibition of FoxM1b is a critical mechanism for suppression of tumour metastasis. |
| تدمد: | 1757-4684 1757-4676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::120a26727439f25bb56202aca71dfac3Test https://doi.org/10.1002/emmm.201000107Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....120a26727439f25bb56202aca71dfac3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574684 17574676 |
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