NDLI: RETRACTED ARTICLE: Regulation of metastasis of pediatric multiple myeloma by MMP13

Content Provider	Springer Nature Link
Author	Wang, Xiaoru Cao, Xiaocang
Copyright Year	2014
Abstract	The molecular mechanism underlying metastasis of pediatric multiple myeloma (MM) remains elusive. Here, we showed that the levels of MMP13 are significantly higher in MM from young patients than those from adult patients. Moreover, a strong correlation of the MMP13 and phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels was detected in MM from young patients. To prove a causal link between activation of fibroblast growth factor receptors (FGFR) signaling pathway and MMP13 expression, we used a human MM line, RPMI-8226 (8226), to study the underlying molecular basis. We found that FGF1-induced FGFR4 phosphorylation in 8,226 cells resulted in significant activation of MMP13, and consequently, an increase in cancer invasiveness. FGFR4 inhibition in 8,226 cells abolished FGF1-stimulated MMP13 expression, suggesting that activation of FGFR signaling pathway in MM may promote cancer metastasis by inducing MMP13 expression. To define the signaling cascades downstream of FGFR4 activation for MMP13 activation, we applied specific inhibitors for PI3K, Jun N-terminal kinase (JNK), and ERK/MAPK, respectively, to the FGF1-stimulated 8,226 cells. We found that only inhibition of ERK1/2 significantly decreased the activation of MMP13 in response to FGF stimulation, suggesting that activation of FGFR signaling may activate ERK/MAPK, rather than JNK or PI3K pathway to activate MMP13 expression in 8,226 cells. Our study thus highlights FGFR4 signaling pathway and MMP13 as novel therapeutic targets for MM.
Starting Page	8715
Ending Page	8720
Page Count	6
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	35
Issue Number	9
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-05-29
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Multiple myeloma FGFR4 MMP13 ERK/MAPK PI3K JNK Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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