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.
Article
in English
| 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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Phosphorylation
/
Physiology
/
Plasmids
/
Protein Kinase C
/
Mouth Neoplasms
/
Carcinoma, Squamous Cell
/
NF-kappa B
/
Tumor Necrosis Factor-alpha
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
International Journal of Oral Science
Year:
2009
Type:
Article
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