Tumor Stroma–Derived Wnt5a Induces Differentiation of Basal Cell Carcinoma of Ptch-Mutant Mice via CaMKII

Abstract

Basal cell carcinoma (BCC) is the most common skin tumor in humans. Although BCCs rarely metastasize, they can cause significant morbidity due to local aggressiveness. Approximately 20% of BCCs show signs of spontaneous regression. The understanding of molecular events mediating spontaneous regression has the potential to reduce morbidity of BCC and, potentially, other

GLI1-dependent transcriptional repression of CYLD in basal cell carcinoma

“…In the current experiment we found epithelial cells from the superficial BCCs to contain Bcl-3 localized in the nucleus (Figure 3a). These results were confirmed by analysing BCC tissue samples from mice expressing constitutively active Smo in the epidermis in response to tamoxifen administration (K5creERT;R26SmoM2; Jeong et al, 2004;Nitzki et al, 2010). As shown in Figure 3b, we detected strong expression of nuclear Bcl-3 protein in both early (45 days post-tamoxifen injection) and full-blown BCC-like lesions (90 days post-tamoxifen injection).…”

“…Induction of BCC in animals was performed as described previously (Nitzki et al, 2010). Briefly, SmoM2 expression was induced 28 days post birth by i.p.…”

Low Dose Ultraviolet B Irradiation Increases Hyaluronan Synthesis in Epidermal Keratinocytes via Sequential Induction of Hyaluronan Synthases Has1–3 Mediated by p38 and Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII) Signaling*

“…CaMKII also appears to be a key mediator in carcinomas inducing keratinocyte differentiation with Wnt5a in regressing tumors (84). Moreover, the hyaluronan-CD44 axis has been indicated to convey signals via CaMKII in head and neck squamous carcinoma cells, causing cytoskeletal rearrangements and promoting migration (85).…”

A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction

“…cDNA synthesis and primer combinations used for quantification of 18S rRNA, Gli1, and 25-hydroxyvitamin D 3 -24-hydroxylase (24-hydroxylase, Cyp24a1) transcripts by quantitative RT-PCR were described previously (17,34,35). Gli1 and Cyp24a1 transcript levels were normalized to the transcript levels of 18S rRNA, after determining the respective amounts by the standard curve method.…”