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KMID : 0606920130210050338
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Biomolecules & Therapeutics
2013 Volume.21 No. 5 p.338 ~ p.342
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Ethacrynic Acid Inhibits Sphingosylphosphorylcholine-Induced Keratin 8 Phosphorylation and Reorganization via Transglutaminase-2 Inhibition
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Byun Hyun-Jung
Kang Kyung-Jin
Park Mi-Kyung
Lee Hye-Ja
Kang June-Hee
Lee Eun-Ji
Kim You-Ri
Kim Hyun-Ji
Kim Young-Woo
Jung Kyung-Chae
Kim Soo-Youl
Lee Chang-Hoon
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Abstract
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Sphingosylphosphorylcholine (SPC) is significantly increased in the malicious ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments in PANC-1 cells. The reorganization contributes to the viscoelasticity of metastatic cancer cells resulting in increased migration. Recently, we reported that transglutaminase-2 (Tgase-2) is involved in SPC-induced K8 phosphorylation and reorganization. However, effects of Tgase-2 inhibitors on SPC-induced K8 phosphorylation and reorganization were not clearly studied. We found that ethacrynic acid (ECA) concentration-dependently inhibited Tgase-2. Therefore, we examined the effects of ECA on SPC-induced K8 phosphorylation and reorganization. ECA concentration-dependently suppressed the SPC-induced phosphorylation and perinuclear reorganization of K8. ECA also suppressed the SPC-induced migration and invasion. SPC induced JNK activation through Tgase-2 expression and ECA suppressed the activation and expression of JNK in PANC-1 cells. These results suggested that ECA might be useful to control Tgase-2 dependent metastasis of cancer cells such as pancreatic cancer and lung cancers.
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KEYWORD
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Sphingosylphosphorylcholine, Transglutaminase-2, Keratin-8 phosphorylation and reorganization, Ethacrynic acid, Migration, Invasion
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