CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex.
- Author:
Aasia O REHMAN
1
;
Cun-yu WANG
Author Information
- Publication Type:Journal Article
- MeSH: Adaptor Proteins, Signal Transducing; antagonists & inhibitors; physiology; B-Cell CLL-Lymphoma 10 Protein; CARD Signaling Adaptor Proteins; antagonists & inhibitors; physiology; Carcinoma, Squamous Cell; pathology; Caspase Inhibitors; Caspases; physiology; Cell Line, Tumor; Chemokine CXCL12; antagonists & inhibitors; physiology; Enzyme Activation; drug effects; Gene Silencing; Genetic Vectors; genetics; Humans; I-kappa B Kinase; drug effects; I-kappa B Proteins; metabolism; Isoenzymes; antagonists & inhibitors; Lentivirus; genetics; Membrane Proteins; antagonists & inhibitors; physiology; Mouth Neoplasms; pathology; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; NF-KappaB Inhibitor alpha; NF-kappa B; antagonists & inhibitors; physiology; Neoplasm Invasiveness; Neoplasm Proteins; antagonists & inhibitors; physiology; Phosphorylation; Plasmids; genetics; Protein Kinase C; antagonists & inhibitors; Receptors, CXCR4; physiology; Tumor Necrosis Factor-alpha; pharmacology
- From: International Journal of Oral Science 2009;1(3):105-118
- CountryChina
- Language:English
-
Abstract:
AIMTo determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF-kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion.
METHODOLOGYA lentivirus-based knockdown approach was utilized to deplete gene expression. NF-kappaB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA).
RESULTSWe 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.
CONCLUSIONThe 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.
