Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours

Moubayed, Noemi; Weichenthal, Michael; Harder, Jürgen; Wandel, Elke; Sticherling, Michael; Gläser, Regine

doi:10.1007/s00432-006-0164-y

Cited by 71 publications

(68 citation statements)

References 22 publications

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“…Highest psoriasin expression was seen in differentiated cellular layers, which is in line with absent psoriasin expression in undifferentiated keratinocytes (19) and undifferentiated tumour cells of basal cell carcinoma (20). The distribution of RNase 7, hBD-2 and -3 is in concordance with their proposed function as a chemical shield against pathogens, as the first contact with microorganisms occurs in the stratum corneum (1,2).…”

Section: Discussionsupporting

confidence: 57%

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Wittersheim

Cordes

Meyer‐Hoffert

et al. 2013

Experimental Dermatology

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Antimicrobial peptides (AMP) are key players in the skin's defense system. Previous observations suggest a site-and age-dependent expression of individual AMP. We investigated the expression and secretion patterns of four important AMP in a representative collective of healthy human skin samples. Levels of psoriasin, RNase 7 and hBD-3 expression -assessed by immunohistochemistry -varied between different body localisations. Older individuals expressed hBD-2 more frequently. No gender-related expression was observed. The in vivo secretion of psoriasin, measured in skin washing fluids using ELISA, was related to body localisation and age, whereas RNase 7 secretion showed no significant differences regarding these variables. HBD-2 and -3 secretion could not be detected. Our findings suggest the usage of control samples matching localisation and approximate age (in the case of hBD-2) for comparative immunohistochemical analysis. To avoid bias through great interindividual differences, sufficient large collectives should be used for in vivo secretion analyses.Abbreviations: AMP, antimicrobial peptides; ELISA, enzyme-linked immunosorbent assay; hBD, human b-defensin; IHC-Score, immunohistochemistry-Score; RNase, ribonuclease.

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Section: Discussionsupporting

confidence: 57%

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Wittersheim

Cordes

Meyer‐Hoffert

et al. 2013

Experimental Dermatology

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“…In humans, there are two genes-S100A7 (psoriasin) and S100A15 (koebnerisin)-that correspond to the single s100a7a15 ortholog in mice. Psoriasin and koebnerisin have been previously shown to be up-regulated in human epithelial skin tumors (Moubayed et al 2007;Hattinger et al 2013). Here we show that S100A7 and S100A15 expression is increased in cutaneous SCCs compared with normal skin and epithelial BCCs.…”

Section: Discussionmentioning

confidence: 99%

Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos

et al. 2013

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Skin squamous cell carcinomas (SCCs) are the second most prevalent skin cancers. Chronic skin inflammation has been associated with the development of SCCs, but the contribution of skin inflammation to SCC development remains largely unknown. In this study, we demonstrate that inducible expression of c-fos in the epidermis of adult mice is sufficient to promote inflammation-mediated epidermal hyperplasia, leading to the development of preneoplastic lesions. Interestingly, c-Fos transcriptionally controls mmp10 and s100a7a15 expression in keratinocytes, subsequently leading to CD4 T-cell recruitment to the skin, thereby promoting epidermal hyperplasia that is likely induced by CD4 T-cell-derived IL-22. Combining inducible c-fos expression in the epidermis with a single dose of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) leads to the development of highly invasive SCCs, which are prevented by using the anti-inflammatory drug sulindac. Moreover, human SCCs display a correlation between c-FOS expression and elevated levels of MMP10 and S100A15 proteins as well as CD4 T-cell infiltration. Our studies demonstrate a bidirectional cross-talk between premalignant keratinocytes and infiltrating CD4 T cells in SCC development. Therefore, targeting inflammation along with the newly identified targets, such as MMP10 and S100A15, represents promising therapeutic strategies to treat SCCs.

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“…In addition, increased S100A7 expression has been reported in nearly all types of SCC tissues as well as adenocarcinomas of the breast (3)(4)(5)(6)(7). Our recent works uncovered that the S100A7 acted as a dual regulator in promoting proliferation and suppressing differentiation in several SCC cells (8)(9)(10)(11).…”

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confidence: 77%

YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

Kong

Shao

et al. 2017

Molecular Cancer Research

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In several squamous cell carcinoma (SCC) cells, it has been previously observed that induction of the S100 calcium-binding protein A7 (S100A7) is repressed by YAP via the Hippo pathway. This report now demonstrates that S100A7 also represses YAP expression and activity by DNp63 in cancer cells. Stable overexpression of S100A7 activates the NFkB pathway and inhibits the expression of DNp63. Caffeic acid phenethyl ester (CAPE), as a specific inhibitor of NFkB, counteracts the inhibitory effect of S100A7 on the expression of DNp63 and its target genes. Depletion of S100A7 significantly promotes DNp63 expression. These data indicate that S100A7 acts as a suppressor of DNp63. Mechanistic examination finds that DNp63 not only directly binds to the region of YAP promoter and induces its expression, but also inhibits the Hippo pathway and enhances YAP activity. Importantly, either the positive correlation between S100A7 and YAP phosphorylation at S127 or the negative correlation between S100A7 and DNp63 is also observed in skin SCC tissues. Chemosensitivity analysis reveals that S100A7 enhances cancer cells' resistance by inhibition of YAP expression and activity. These results demonstrate that S100A7 is an upstream modulator of the Hippo pathway and extend our understanding of S100A7 functions in cancer.Implications: S100A7 is a new upstream regulator of the Hippo signaling pathway and reduces chemosensitivity of SCC cells through inhibitions of YAP expression and activity.

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Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours

Abstract: Similar to the findings in breast and bladder cancer, the up-regulation of psoriasin might play a role in the progression of skin cancer. The expression of psoriasin in human skin tumours seems to be independent from differentiation and inflammation.

Cited by 71 publications

References 22 publications

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos

YAP Expression and Activity Are Suppressed by S100A7 via p65/NFκB-mediated Repression of ΔNp63

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