期刊
ONCOGENE
卷 32, 期 12, 页码 1594-1600出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.151
关键词
Trop-2; human tumours; cell growth; cell signalling
资金
- Fondazione of the Cassa di Risparmio della Provincia di Chieti
- ABO Foundation [CH01D0081]
- Fondazione compagnia di San Paolo
- Italian Ministry of Health [RicOncol RF-EMR-2006-361866]
- Italian Foundation for Cancer Research (FIRC, Italy)
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Our findings show that upregulation of a wild-type Trop-2 has a key controlling role in human cancer growth, and that tumour development is quantitatively driven by Trop-2 expression levels. However, little is known about the regulation of expression of the TROP2 gene. Hence, we investigated the TROP2 transcription control network. TROP2 expression was shown to depend on a highly interconnected web of transcription factors: TP63/TP53L, ERG, GRHL1/Get-1 (grainyhead-like epithelial transactivator), HNF1A/TCF-1 (T-cell factor), SPI1/PU.1, WT (Wilms' tumour) 1, GLIS2, AIRE (autoimmune regulator), FOXM1 (forkhead box M1) and FOXP3, with HNF4A as the major network hub. TROP2 upregulation was shown to subsequently drive the expression and activation of CREB1 (cyclic AMP-responsive-element binding protein), Jun, NF-kappa B, Rb, STAT1 and STAT3 through induction of the cyclin D1 and ERK (extracellular signal regulated kinase)/MEK (MAPK/ERK kinase) pathways. Growth-stimulatory signalling through NF-kappa B, cyclin D1 and ERK was shown to require an intact Trop-2 cytoplasmic tail. Network hubs and interacting partners are co-expressed with Trop-2 in primary human tumours, supporting a role of this signalling network in cancer growth. Oncogene (2013) 32, 1594-1600; doi:10.1038/onc.2012.151; published online 7 May 2012
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