Biomol Ther.  2013 Sep;21(5):338-342.

Ethacrynic Acid Inhibits Sphingosylphosphorylcholine-Induced Keratin 8 Phosphorylation and Reorganization via Transglutaminase-2 Inhibition

• Byun HJ
• Kang KJ
• Park MK
• Lee HJ
• Kang JH
• Lee EJ
• Kim YR
• Kim HJ
• Kim YW
• Jung KC
• Kim SY
• Lee CH

Abstract

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.

Keyword

Sphingosylphosphorylcholine; Transglutaminase-2; Keratin-8 phosphorylation and reorganization; Ethacrynic acid; Migration; Invasion

MeSH Terms

Ascites
Ethacrynic Acid*
Humans
Keratin-8*
Lung Neoplasms
Neoplasm Metastasis
Pancreatic Neoplasms
Phosphorylation*
Ethacrynic Acid
Keratin-8