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Nogo-B (Reticulon-4B) functions as a negative regulator of the apoptotic pathway through the interaction with c-FLIP in colorectal cancer cells.
Kawaguchi, Nao; Tashiro, Keitaro; Taniguchi, Kohei; Kawai, Masaru; Tanaka, Keitaro; Okuda, Junji; Hayashi, Michihiro; Uchiyama, Kazuhisa.
Afiliação
  • Kawaguchi N; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
  • Tashiro K; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan. Electronic address: sur085@osaka-med.ac.jp.
  • Taniguchi K; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
  • Kawai M; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
  • Tanaka K; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
  • Okuda J; Osaka Medical College Hospital Cancer Center, Osaka, Japan.
  • Hayashi M; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
  • Uchiyama K; Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
Biochim Biophys Acta Mol Basis Dis ; 1864(8): 2600-2609, 2018 Aug.
Article em En | MEDLINE | ID: mdl-29684585
Nogo-B is a member of the Nogo/Reticulon-4 family and has been reported to be an inducer of apoptosis in certain types of cancer cells. However, the role of Nogo-B in human cancer remains less understood. Here, we demonstrated the functions of Nogo-B in colorectal cancer cells. In clinical colorectal cancer specimens, Nogo-B was obviously overexpressed, as determined by immunohistochemistry; and Western blot analysis showed its expression level to be significantly up-regulated. Furthermore, knockdown of Nogo-B in two colorectal cancer cell lines, SW480 and DLD-1, by transfection with si-RNA (siR) resulted in significantly reduced cell viability and a dramatic increase in apoptosis with insistent overexpression of cleaved caspase-8 and cleaved PARP. The transfection with Nogo-B plasmid cancelled that apoptosis induced by siRNogoB in SW480 cells. Besides, combinatory treatment with siR-Nogo-B/staurosporine (STS) or siR-Nogo-B/Fas ligand (FasL) synergistically reduced cell viability and increased the expression of apoptotic signaling proteins in colorectal cancer cells. These results strongly support our contention that Nogo-B most likely played an oncogenic role in colorectal cancer cells, mainly by negatively regulating the extrinsic apoptotic pathway in them. Finally, we revealed that suppression of Nogo-B caused down-regulation of c-FLIP, known as a major anti-apoptotic protein, and activation of caspase-8 in the death receptor pathway. Interaction between Nogo-B and c-FLIP was shown by immunoprecipitation and immunofluorescence studies. In conclusion, Nogo-B was shown to play an important negative role in apoptotic signaling through its interaction with c-FLIP in colorectal cancer cells, and may thus become a novel therapeutic target for colorectal cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Transdução de Sinais / Apoptose / Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD / Proteínas Nogo / Proteínas de Neoplasias Limite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Transdução de Sinais / Apoptose / Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD / Proteínas Nogo / Proteínas de Neoplasias Limite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão País de publicação: Holanda