TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis.
Proc Natl Acad Sci U S A
; 116(26): 13026-13035, 2019 06 25.
Article
em En
| MEDLINE
| ID: mdl-31182586
ABSTRACT
Pancreatic cancer typically spreads rapidly and has poor survival rates. Here, we report that the calcium-activated chloride channel TMEM16A is a biomarker for pancreatic cancer with a poor prognosis. TMEM16A is up-regulated in 75% of cases of pancreatic cancer and high levels of TMEM16A expression are correlated with low patient survival probability. TMEM16A up-regulation is associated with the ligand-dependent EGFR signaling pathway. In vitro, TMEM16A is required for EGF-induced store-operated calcium entry essential for pancreatic cancer cell migration. TMEM16A also has a profound impact on phosphoproteome remodeling upon EGF stimulation. Moreover, molecular actors identified in this TMEM16A-dependent EGFR-induced calcium signaling pathway form a gene set that makes it possible not only to distinguish neuro-endocrine tumors from other forms of pancreatic cancer, but also to subdivide the latter into three clusters with distinct genetic profiles that could reflect their molecular underpinning.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Biomarcadores Tumorais
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Sinalização do Cálcio
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Carcinoma Ductal Pancreático
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Fator de Crescimento Epidérmico
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Anoctamina-1
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Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2019
Tipo de documento:
Article