Browsing by Author "Lin, Yuh-Charn"

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PSPC1 mediates TGF-beta 1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis
(2018-04-01)
Yeh, Hsi-Wen
;
Hsu, En-Chi
;
Lee, Szu-Shuo
;
Lang, Yaw-Dong
;
Lin, Yuh-Charn
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.