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Cancers display a diverse set of cellular defects, which are thought to be elicited by multiple genetic mutations. In this study, we show that when a single adherens junction protein, [alpha]-catenin, is removed by conditional targeting, the entire skin epidermis systematically transforms to a hyperproliferative, invasive tissue replete with inflammation. Transcriptional profiling and biochemical analyses reveal that [alpha]-catenin ablation is accompanied by activation of NF-[kappa]B and its proinflammatory target genes, along with genes involved in proliferation, wound healing, angiogenesis, and metastasis. Many of these alterations occur in vitro and in the embryo, and thus seem at least partly to be intrinsic to the loss of [alpha]-catenin. We show that reductions in [alpha]-catenin, activation of NF-[kappa]B, and inflammation are common features of human squamous cell carcinomas of the skin. cancer | inflammation | E-cadherin

During epithelial sheet formation, linear actin cables assemble at nascent adherens junctions. This process requires a-catenin and actin polymerization, although the underlying mechanism is poorly understood. Here, we show that formin-1 interacts with a-catenin, localizes to adherens junctions and nucleates unbranched actin filaments. Furthermore, disruption of the a-catenin-formin-1 interaction blocks assembly of radial actin cables and perturbs intercellular adhesion. A fusion protein of the ß-catenin-binding domain of a-catenin with the actin polymerization domains of formin-1 rescues formation of adherens junctions and associated actin cables in a-catenin-null keratinocytes. These findings provide new insight into how a-catenin orchestrates actin dynamics during intercellular junction formation. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is an aggressive tumor with a poor prognosis due to late diagnosis and loco-regional metastasis. Partial or more complete epithelial–mesenchymal transition (EMT) plays a role in tumor progression; however, it remains a challenge to observe the EMT in vivo, due to its transient nature. Here, we developed a novel catulin promoter-based reporter system that allows us to isolate and characterize in vivo a small fraction of invasive cancer cells. The analyses of tumors revealed that Catulin-green fluorescent protein (GFP)-positive cells were enriched in clusters of cells at the tumor invasion front. A functional genomic study unveiled genes involved in cellular movement and invasion providing a molecular profile of HNSCC invasive cells. This profile overlapped partially with the expression of signature genes related to the partial EMT available from the single cell analysis of human HNSCC specimens, highlighting the relevance of our data to the clinical disease progression state. Interestingly, we also observed upregulations of genes involved in axonal guidance—L1 cell adhesion molecule (L1CAM), neuropilin-1, semaphorins, and ephrins, indicating potential interactions of cancer cells and neuronal components of the stroma. Taken together, our data indicated that the catulin reporter system marked a population of invasive HNSCC cells with a molecular profile associated with cancer invasion. [ABSTRACT FROM AUTHOR]

Recent developments of the investigations on the molecular basis of anhidrotic ectodermal dysplasia are reviewed. Identification of the major product of the EDA gene (ectodysplasin A), a protein belonging to a group of TNF ligands, and molecular cloning of the cDNA, encoding its receptor (EDAR), a member of the TNF receptor family, are presented. The role of an alternative EDA receptor, localised on the X chromosome (XEDAR) in the developmental control of the differentiation of skin appendages, is discussed. Recent findings have elucidated the cause of the autosomal forms of EDA, both dominant and recessive, and indicated an important role of a signal transduction pathway involving a protein product of the NEMO gene and the transcription factor NFkappaB in the differentiation of skin appendages.