The Multiple Facets of Dermcidin in Cell Survival and Host Defense

Schittek, Birgit

doi:10.1159/000336844

Cited by 83 publications

(82 citation statements)

References 152 publications

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“…Indeed, applying our classification methods to AJCC stage I–II patients revealed that the stage II patients with DCD levels <2.98 μg/ml are more likely to develop metastasis during follow‐up (80% correctly classified instances). Elevated DCD levels have also been found in the serum of breast cancer patients collected at the time of diagnosis,44 although DCD expression in these tumor cells is associated with advanced clinical stage and poor disease prognosis 45. By contrast, in our group of melanoma patients, lower level of DCD was a significant factor that predicted a metastatic outcome in AJCC stage II patients.…”

Section: Discussionmentioning

confidence: 53%

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Ortega-Martinez

Gardeazábal

Erramuzpe

et al. 2016

Intl Journal of Cancer

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Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I–II patients may still develop metastasis during follow‐up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow‐up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease‐free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early‐stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 μg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival.

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Section: Discussionmentioning

confidence: 53%

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Ortega-Martinez

Gardeazábal

Erramuzpe

et al. 2016

Intl Journal of Cancer

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“…There is a growing interest in dermcidin since its discovery in 2001 (23). The role of DCD in cancer proliferation is of particular interest as the DCD-derived peptide Y-P30 has been shown to provide a cancer-associated function in the prostate (26).…”

Section: Resultsmentioning

confidence: 99%

“…In each analysis, we also found peptide fragments that corresponded to the 30 aa proteolysisinducing factor (PIF) core, 13 aa propeptide, and 47 aa DCD-1 peptide region of the poorly characterized dermcidin protein (DCD) (Fig. 4A) (23). LC-MS/MS analyses also identified a 12-kDa band as DCD itself (SI Appendix, Fig.…”

Section: Significancementioning

confidence: 89%

Seriniquinone, a selective anticancer agent, induces cell death by autophagocytosis, targeting the cancer-protective protein dermcidin

Trzoss

Fukuda

Costa-Lotufo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Natural products continue to provide vital treatment options for cancer. Although their translation into chemotherapeutics is complex, collaborative programs continue to deliver productive pipelines for cancer chemotherapy. A new natural product, seriniquinone, isolated from a marine bacterium of the genus Serinicoccus, demonstrated potent activity over a select set of tumor cell lines with particular selectivity toward melanoma cell lines. Upon entering the cell, its journey began by localization into the endoplasmic reticulum. Within 3 h, cells treated with seriniquinone underwent cell death marked by activation of autophagocytosis and gradually terminated through a caspase-9 apoptotic pathway. Using an immunoaffinity approach followed by multipoint validation, we identified the target of seriniquinone as the small protein, dermcidin. Combined, these findings revealed a small molecule motif in parallel with its therapeutic target, whose potential in cancer therapy may be significant. This discovery defines a new pharmacophore that displayed selective activity toward a distinct set of cell lines, predominantly melanoma, within the NCI 60 panel. This selectivity, along with the ease in medicinal chemical modification, provides a key opportunity to design and evaluate new treatments for those cancers that rely on dermcidin activity. Further, the use of dermcidin as a patient preselection biomarker may accelerate the development of more effective personalized treatments.mode of action | chemical biology | drug discovery | marine natural products | cancer

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“…Esta proteína foi primeiramente identificada em glândulas sudoríparas (Schittek;Hipfel et al, 2001), contribuindo para a primeira linha de defesa da pele por constituir uma barreira constante que recobre o epitélio (Schittek;Paulmann et al, 2008;Wiesner e Vilcinskas, 2010). Contudo, posteriormente, essa proteína foi encontrada também em células neuronais e leucócitos de sangue periférico (Schittek, 2012).…”

Section: Discussionunclassified

“…Contudo, posteriormente, essa proteína foi encontrada também em células neuronais e leucócitos de sangue periférico (Schittek, 2012).…”

Section: Discussionunclassified

Mecanismos moleculares envolvidos em citoproteção e transformação maligna de células-beta pancreáticas

Terra¹

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Mecanismos moleculares envolvidos em citoproteção e transformação maligna de células-beta pancreáticasT e r r a , Le tíc ia F e r r ei r a T 3 2 3 m M e c a n i s m o s m o l e c u l a r e s e n v o l v i d o s e m c i t o p r o t e ç ã o e tr a nsfor maç ã o ma ligna de c é l u l a s -b e t a p anc r e á tic a s / Le tí ci a F er r e ir a T e r r a . --Sã o P aulo , 2 0 13 . 1 9 4p .T ese ( do utor a d o ) -I nstituto d e Químic a d a Unive r sid a d e de S ão P a ulo . De pa r ta me nto de B io químic a .Or i enta d or : So ga ya r , Ma r i Cle id e . C o-o r ie nta do r : La b r iol a, Le tíc ia .1 . B io lo gia c e lula r 2 . Ca nc e r 3. Ap op to se : P a tol ogia 4 . Dia b e te s M el litus I . T . I I . S oga ya r , M ar i Cle id e , o r ie nta do r . I I I . La b r io la , Letí ci a, o r ie nta d o r . AgradecimentosÀ Profa. Dra. Mari C. Sogayar, pela orientação e por todo o apoio. Pelos conselhos, sugestões e críticas, sempre mostrando sua opinião em todos os assuntos. Por ter aberto as portas do laboratório para mim oito anos atrás e me introduzido ao fantástico mundo da ciência, favorecendo meu amadurecimento de incontáveis formas. Obrigada ainda por permitir que o laboratório possua o ambiente agradável e receptivo que apresenta, fazendo dele nossa segunda casa. À Profa. Dra. Leticia Labriola, pela co-orientação desta tese. Por ter me orientado no meu trabalho de conclusão de curso na faculdade, pelas discussões e sugestões.Sinto-me feliz em ter podido presenciar e fazer parte, mesmo que pequena, da evolução de sua carreira. Obrigada por me acalmar em todos os momentos que tudo que precisamos é uma palavra amiga, principalmente quando um resultado importante dá errado, um artigo retorna ou uma bolsa é recusada.Ao Prof. Dr. Décio L. Eizirik e à Dra. Alessandra K. Cardozo, por terem me recebido em seu laboratório na Université Libre de Bruxelles, por toda a preocupação, conversas e ajuda que me forneceram durante os seis meses que fiquei por lá, pelo contato que mantivemos e ainda mantemos desde minha volta, por me mostrarem a ciência do outro lado do mundo, por terem me apresentado a inúmeras pessoas que com certeza serão importantes em algum momento no meu futuro e por terem me levado a diversos seminários e reuniões que abriram ainda mais a minha mente. À Alessandra pela supervisão e pelas discussões constantes, conseguindo tornar o meu dia-a-dia o mais produtivo que ele poderia ser. Ao Décio pelos conselhos, recomendações e sugestões, não somente sobre o tempo que passei com eles, como também sobre meu futuro, penso nisso constantemente.Obrigada a ambos por me fazerem sentir como se sempre tivesse sido parte do Laboratory of Experimental Medicine, e por fazer dele um lugar para onde eu sempre poderei voltar.Aos meus colaboradores do INCOR, Prof. Dr. Edécio C. Neto, por permitir a realização de parte deste trabalho em seu laboratório e disponibilizar seus aparelhos para minha utilização; e à Dra. Priscila C. Teixeira, por me ensinar tudo relacionado ao 2D-DIGE, da técnica à análise de resultados. À...

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The Multiple Facets of Dermcidin in Cell Survival and Host Defense

Cited by 83 publications

References 152 publications

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I–II early‐stage melanoma

Seriniquinone, a selective anticancer agent, induces cell death by autophagocytosis, targeting the cancer-protective protein dermcidin

Mecanismos moleculares envolvidos em citoproteção e transformação maligna de células-beta pancreáticas

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