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CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex / 国际口腔科学杂志·英文版
International Journal of Oral Science ; (4): 105-118, 2009.
Artículo en Inglés | WPRIM | ID: wpr-269712
ABSTRACT
<p><b>AIM</b>To determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF-kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion.</p><p><b>METHODOLOGY</b>A lentivirus-based knockdown approach was utilized to deplete gene expression. NF-kappaB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA).</p><p><b>RESULTS</b>We show that the activation of NF-kappaB by CXCR4 occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1 alpha mediated invasion of OSCC.</p><p><b>CONCLUSION</b>The CBM complex plays a critical role in CXCR4-induced NF-kappaB activation in OSCC. Targeting molecular components of the NF-kappaB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1 alpha.</p>
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Patología / Farmacología / Fosforilación / Fisiología / Plásmidos / Proteína Quinasa C / Neoplasias de la Boca / Carcinoma de Células Escamosas / FN-kappa B / Factor de Necrosis Tumoral alfa Tipo de estudio: Estudio pronóstico Límite: Humanos Idioma: Inglés Revista: International Journal of Oral Science Año: 2009 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Patología / Farmacología / Fosforilación / Fisiología / Plásmidos / Proteína Quinasa C / Neoplasias de la Boca / Carcinoma de Células Escamosas / FN-kappa B / Factor de Necrosis Tumoral alfa Tipo de estudio: Estudio pronóstico Límite: Humanos Idioma: Inglés Revista: International Journal of Oral Science Año: 2009 Tipo del documento: Artículo