The cellular changes during an epithelial-mesenchymal transition (EMT) largely rely on global changes in gene expression orchestrated by transcription factors. Tead transcription factors and their transcriptional co-activators Yap and Taz have been previously implicated in promoting an EMT; however, their direct transcriptional target genes and their functional role during EMT have remained elu...

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Currently, the affected eye is either removed by surgery (enucleation) or treated with radiation therapy. However, there is no effective treatment for metastatic UM, which frequently spreads to the liver via a haematogenous route. The majority (~80%) of UM cases are driven by mutually exclusive mutations in GNAQ or GNA11, ...

OBJECTIVE To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation. APPROACH AND RESULTS We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocki...

The Hippo pathway was initially identified in Drosophila by genetic mosaic screens for tumor suppressor genes. Researches indicated that the Hippo pathway is a key regulator of organ size and is conserved during evolution. Furthermore, studies of mouse models and clinical samples demonstrated the importance of Hippo pathway dysregulation in human cancer development. In addition, the Hippo pathw...

The YAP1 gene of Saccharomyces cerevisiae encodes a bZIP-containing transcription factor that is essential for the normal response of cells to oxidative stress. Under stress conditions, the activity of yAP-1 is increased, leading to the induced expression of a number of target genes encoding protective enzymes or molecules. We have examined the mechanism of this activation. Upon imposition of o...

The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the...

Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor that is methylated in many human cancers, including hepatocellular carcinoma (HCC). RASSF1A has been shown to suppress tumors via activation of the Hippo tumor suppressor pathway, including mammalian STE20-like kinase (MST). Amphiregulin (AREG), a target gene for Yes-associated protein (YAP), is a known oncogenic componen...

Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor and the methylation thereof is known to be involved in many human cancers including hepatocellular carcinoma (HCC). RASSF1A has been shown to suppress tumors via activation of components of the Hippo tumor suppressor pathway, including mammalian STE20-like kinase (MST). Amphiregulin (AREG), a target gene for Yes-associate...

The Yes-associated protein (YAP) transcription coactivator is a key regulator of organ size and a candidate human oncogene. YAP is inhibited by the Hippo pathway kinase cascade, at least in part via phosphorylation of Ser 127, which results in YAP 14-3-3 binding and cytoplasmic retention. Here we report that YAP is phosphorylated by Lats on all of the five consensus HXRXXS motifs. Phosphorylati...