The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter.

Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity.

Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.

Background: Epithelial-to-mesenchymal transition (EMT) enhances motility, stemness, chemoresistance and metastasis. Little is known about how various pathways coordinate to elicit EMT's different functional aspects in non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) has been previously correlated with EMT transcription factor ZEB1 in NSCLC and imparts resistance against anti-folate chemotherapy.

Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers.

Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24 differentiated cells, and attenuated migration and sphere-formation.

Promoter cloning and characterization of the human programmed cell death protein 4 (pdcd4) gene: evidence for ZBP-89 and Sp-binding motifs as essential Pdcd4 regulators.

Pdcd4 (programmed cell death protein 4) is an important novel tumour suppressor inhibiting transformation, translation, invasion and intravasation, and its expression is down-regulated in several cancers. However, little is known about the transcriptional regulation and the promoter of this important tumour suppressor. So far the following is the first comprehensive study to describe the regulation of Pdcd4 transcription by ZBP-89 (zinc-finger-binding protein 89), besides characterizing the gene promoter.

First evidence that the antimalarial drug artesunate inhibits invasion and in vivo metastasis in lung cancer by targeting essential extracellular proteases.

Despite progress in treatment, progressive non-small cell lung cancer (NSCLC) still limits survival dramatically, and novel therapeutic compounds are needed. Initial investigations suggest that artesunate (ART), an antimalarial drug, has antiproliferative capacities. However, antiinvasive and antimetastatic properties of ART in cancer have never been explored.