Citation
- Authors: Yeh, H. W., Hsu, E. C., Lee, S. S., Lang, Y. D., Lin, Y. C., Chang, C. Y., Lee, S. Y., Gu, D. L., Shih, J. H., Ho, C. M., Chen, C. F., Chen, C. T., Tu, P. H., Cheng, C. F., Chen, R. H., Yang, R. B., Jou, Y. S.
- Year: 2018
- Journal: Nat Cell Biol 20 479-491
- Applications: in vitro / DNA / jetPRIME
- Cell types:
- Name: A549
Description: Human lung carcinoma cells, type II pneumocytes
Known as: A-549 - Name: PC-3
Description: Human prostate carcinoma cells
Known as: PC3, PC 3 - Name: SK-HEP-1
- Name: A549
Abstract
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-beta1 (TGF-beta1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-beta1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-beta1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-beta1 axis in various cancers, we conclude that PSPC1 is a master activator of pro-metastatic switches and a potential target for anti-metastasis drugs.