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Multi-cancer V-ATPase molecular signatures: A distinctive balance of subunit C isoforms in esophageal carcinoma.
Couto-Vieira, Juliana; Nicolau-Neto, Pedro; Costa, Evenilton Pessoa; Figueira, Frederico Firme; Simão, Tatiana de Almeida; Okorokova-Façanha, Anna Lvovna; Ribeiro Pinto, Luis Felipe; Façanha, Arnoldo Rocha.
Afiliação
  • Couto-Vieira J; Laboratório de Biologia Celular e Tecidual, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
  • Nicolau-Neto P; Programa de Carcinogênese Molecular, Instituto Nacional de Câncer - INCA, Rio de Janeiro, RJ, Brazil.
  • Costa EP; Laboratório de Biologia Celular e Tecidual, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
  • Figueira FF; Laboratório de Biologia Celular e Tecidual, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
  • Simão TA; Departamento de Bioquímica, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
  • Okorokova-Façanha AL; Laboratório de Fisiologia e Bioquímica de Microrganismos, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
  • Ribeiro Pinto LF; Programa de Carcinogênese Molecular, Instituto Nacional de Câncer - INCA, Rio de Janeiro, RJ, Brazil; Departamento de Bioquímica, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: lfpinto@inca.gov.br.
  • Façanha AR; Laboratório de Biologia Celular e Tecidual, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil. Electronic address: arnoldo@uenf.br.
EBioMedicine ; 51: 102581, 2020 Jan.
Article em En | MEDLINE | ID: mdl-31901859
BACKGROUND: V-ATPases are hetero-oligomeric enzymes consisting of 13 subunits and playing key roles in ion homeostasis and signaling. Differential expression of these proton pumps has been implicated in carcinogenesis and metastasis. To elucidate putative molecular signatures underlying these phenomena, we evaluated the expression of V-ATPase genes in esophageal squamous cell carcinoma (ESCC) and extended the analysis to other cancers. METHODS: Expression of all V-ATPase genes were analyzed in ESCC by a microarray data and in different types of tumors available from public databases. Expression of C isoforms was validated by qRT-PCR in paired ESCC samples. FINDINGS: A differential expression pattern of V-ATPase genes was found in different tumors, with combinations in up- and down-regulation leading to an imbalance in the expression ratios of their isoforms. Particularly, a high C1 and low C2 expression pattern accurately discriminated ESCC from normal tissues. Structural modeling of C2a isoform uncovered motifs for oncogenic kinases in an additional peptide stretch, and an actin-biding domain downstream to this sequence. INTERPRETATION: Altogether these data revealed that the expression ratios of subunits/isoforms could form a conformational code that controls the H+ pump regulation and interactions related to tumorigenesis. This study establishes a paradigm change by uncovering multi-cancer molecular signatures present in the V-ATPase structure, from which future studies must address the complexity of the onco-related V-ATPase assemblies as a whole, rather than targeting changes in specific subunit isoforms. FUNDING: This work was supported by grants from CNPq and FAPERJ-Brazil.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Subunidades Proteicas / ATPases Vacuolares Próton-Translocadoras Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Subunidades Proteicas / ATPases Vacuolares Próton-Translocadoras Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EBioMedicine Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda