BP180/Collagen XVII: A Molecular View

BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein–protein interactions.

Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway

Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Cell proliferation was negatively correlated with the expression level of COL17 in a concentration-dependent manner in both conventional and three-dimensional (3D) culture systems. The correlation was confirmed by decreased expression of the proliferative marker Ki67 in COL17-expressing cells. In addition, overexpression of COL17 reduced the clonogenicity and growth of the cells. We demonstrated that COL17 affects the AKT/mTOR signaling pathway by deactivation of AKT, mTOR and downstream effectors, particularly 4EBP1. Moreover, mice xenografted with high COL17-expressing cells exhibited delayed tumor progression and prolonged survival time. The high expression of COL17A1 gene encoding COL17 is associated with low-proliferation tumors, extended tumor-free period, and overall survival of breast cancer patients. In conclusion, our results revealed the novel function of COL17 using in vitro and in vivo models and elucidated the related pathway in breast cancer cell growth and proliferation.

Pemphigus and Bullous Pemphigoid

Pemphigus disorders are characterized by acantholysis, whereas pemphigoid disorders are characterized by a dermal-epidermal split. Diagnosis of pemphigus or pemphigoid relies on a combination of positive anti-desmoglein or anti-collagen XVII serology, confirmatory direct immunofluorescence, and clinical features. Treatment for immunobullous disease revolves around various immunosuppressants, most often some combination of rituximab, prednisone, and IVIg. Paraneoplastic pemphigus is characterized by hemorrhagic crusting of the lips with positive indirect immunofluorescence on rat bladder epithelium, which should prompt a search for malignancy. Hailey-Hailey disease is a genetically mediated pemphigus that typically occurs in skin folds and responds to a number of agents including botulinum toxin, topical steroids, and other anecdotal therapies. This review contains 17 figures, 2 tables, and 109 references. Keywords: blister, pemphigus, bullous, rituximab, bullae, prednisone

Pemphigus and Bullous Pemphigoid

Pemphigus disorders are characterized by acantholysis, whereas pemphigoid disorders are characterized by a dermal-epidermal split. Diagnosis of pemphigus or pemphigoid relies on a combination of positive anti-desmoglein or anti-collagen XVII serology, confirmatory direct immunofluorescence, and clinical features. Treatment for immunobullous disease revolves around various immunosuppressants, most often some combination of rituximab, prednisone, and IVIg. Paraneoplastic pemphigus is characterized by hemorrhagic crusting of the lips with positive indirect immunofluorescence on rat bladder epithelium, which should prompt a search for malignancy. Hailey-Hailey disease is a genetically mediated pemphigus that typically occurs in skin folds and responds to a number of agents including botulinum toxin, topical steroids, and other anecdotal therapies. This review contains 17 figures, 2 tables, and 109 references. Keywords: blister, pemphigus, bullous, rituximab, bullae, prednisone