The histone deacetylase inhibitor cambinol prevents acidic pHe-induced anterograde lysosome trafficking independently of sirtuin activity.
The histone deacetylase inhibitor cambinol prevents acidic pHe-induced anterograde lysosome trafficking independently of sirtuin activity.
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DOI：
10.1016/j.bbrep.2015.07.015
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发表时间：
2015-09-01
影响因子：
2.7
通讯作者：
Cardelli, James A
中科院分区：
文献类型：
--
作者：
Dykes, Samantha S;Friday, Ellen;Cardelli, James A
Common features of the solid tumor microenvironment, such as acidic extracellular pH and growth factors, are known to induce the redistribution of lysosomes from a perinuclear region to a position near the plasma membrane. Lysosome/plasma membrane juxtaposition facilitates invasion by allowing for the release of lysosomal proteases, including cathepsin B, which contribute to matrix degradation. In this study we identified the sirtuin 1/sirtuin 2 (SIRT1/2) inhibitor cambinol acts as a drug that inhibits lysosome redistribution and tumor invasion. Treatment of cells with cambinol resulted in a juxtanuclear lysosome aggregation (JLA) similar to that seen upon treatment with the PPARgamma agonist, troglitazone (Tro). Like Tro, cambinol required the activity of ERK1/2 in order to induce this lysosome clustering phenotype. However, cambinol did not require the activity of Rab7, suggesting that this drug causes JLA by a mechanism different from what is known for Tro. Additionally, cambinol-induced JLA was not a result of autophagy induction. Further investigation revealed that cambinol triggered JLA independently of its activity as a SIRT1/2 inhibitor, suggesting that this drug could have effects in addition to SIRT1/2 inhibition that could be developed into a novel anti-cancer therapy.
