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-β1 (TGF-β1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-β1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-β1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-β1 axis in various cancers, we conclude that PSPC1 is a master activator of pro-metastatic switches and a potential target for anti-metastasis drugs.

We formulate and prove a log-algebraicity theorem for arbitrary rank Drinfeld modules defined over the polynomial ring F_q[theta]. This generalizes results of Anderson for the rank one case. As an application we show that certain special values of Goss L-functions are linear forms in Drinfeld logarithms and are transcendental.Comment: 21 page

The N1-selective allylation of indoles with allylic alcohols has been accomplished by synergistic functions of palladium catalysts and titanium tetraisopropoxide.

A method is reported for the catalytic direct coupling of allylic alcohols and nitroalkanes. In the allylation process, the synergistic action of palladium complexes and titanium(IV) alkoxide facilitates the formation of nitronate and π-allylpalladium intermediate. In the cases of reluctant allylations, typically with sterically demanding nitroalkanes, we found the addition of substoichiometric amount of DBU greatly facilitates the desired transformation. We also accomplished a total synthesis of (±)-adalinine through a homoallyl nitroalkane derived from Seebach's reagent.