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Title 

Elevation of intracellular cyclic AMP inhibits NF-κB-mediated thymosin β4 expression in melanoma cells

Authors 

A KimM SonK I KimY YangEun Young SongH G LeeJ S Lim

Publisher 

Elsevier

Issue Date 

2009

Citation 

Experimental Cell Research, vol. 315, no. 19, pp. 3325-3335

Keywords 

Cyclic AMPE-cadherinEMTMetastasisMMPN-cadherinThymosin β4

Abstract 

Thymosin β4 (Tβ4) is a major actin-sequestering protein that has been implicated in the growth, survival, motility, and metastasis of certain tumors and is considered an indicator for malignant progression. Therefore, identifying compounds that can downregulate Tβ4 expression is very important for the development of anti-cancer chemotherapies. In this study, we investigated the effects of elevated cAMP on Tβ4 expression and the metastatic potential of murine B16 melanoma cells. In addition, we also dissected the mechanism underlying cAMP-mediated Tβ4 suppression. We found that treatment with the cAMP-inducing compounds α-MSH (α-melanocyte stimulating hormone) and IBMX (3-isobutyl-1-methylxanthine) significantly suppressed Tβ4 expression and regulated EMT-associated genes through the suppression of NF-κB activation in B16F10 cells. Along with decreased Tβ4 expression, the in vitro invasiveness and anchorage-independent growth in a semi-solid agar of these cells were also inhibited. In animal experiments, the metastatic potential of the α-MSH- or IBMX-treated B16F10 melanoma cells was decreased compared to untreated control cells. Collectively, our data demonstrate that elevated intracellular cAMP significantly suppresses Tβ4 expression and reduces MMP-9 activity, which leads to decreased metastatic potential. Moreover, suppression of NF-κB activation by α-MSH or IBMX is critical for inhibiting Tβ4 expression.

ISSN 

0014-4827

Link 

http://dx.doi.org/10.1016/j.yexcr.2009.05.024

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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