期刊
NATURE CELL BIOLOGY
卷 20, 期 4, 页码 479-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41556-018-0062-y
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资金
- Academia Sinica
- Ministry of Science and Technology (MOST) [106-0210-01-15-02]
- MOST of Taiwan [1062321B001051, 1042320B001009MY3]
Activation of metastatic reprogramming is critical for tumour metastasis. However, more detailed knowledge of the underlying mechanism is needed to enable targeted intervention. Here, we show that paraspeckle component 1 (PSPC1), identified in an aberrant 13q12.11 locus, is upregulated and associated with poor survival in patients with cancer. PSPC1 promotes tumorigenesis, epithelial-to-mesenchymal transition (EMT), stemness and metastasis in multiple cell types and in spontaneous mouse cancer models. PSPC1 is the master activator for transcription factors of EMT and stemness and accompanies c-Myc activation to facilitate tumour growth. PSPC1 increases transforming growth factor-ss 1 (TGF-ss 1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-ss 1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-ss 1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-ss 1 axis in various cancers, we conclude that PSPC1 is a master activator of prometastatic switches and a potential target for anti-metastasis drugs.
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