Ethacrynic Acid Inhibits Sphingosylphosphorylcholine-Induced Keratin 8 Phosphorylation and Reorganization via Transglutaminase-2 Inhibition.
- Author:
Hyun Jung BYUN
1
;
Kyung Jin KANG
;
Mi Kyung PARK
;
Hye Ja LEE
;
June Hee KANG
;
Eun Ji LEE
;
You Ri KIM
;
Hyun Ji KIM
;
Young Woo KIM
;
Kyung Chae JUNG
;
Soo Youl KIM
;
Chang Hoon LEE
Author Information
1. College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea. uatheone@dongguk.edu
- Publication Type:Original Article
- Keywords:
Sphingosylphosphorylcholine;
Transglutaminase-2;
Keratin-8 phosphorylation and reorganization;
Ethacrynic acid;
Migration;
Invasion
- MeSH:
Ascites;
Ethacrynic Acid*;
Humans;
Keratin-8*;
Lung Neoplasms;
Neoplasm Metastasis;
Pancreatic Neoplasms;
Phosphorylation*
- From:Biomolecules & Therapeutics
2013;21(5):338-342
- CountryRepublic of Korea
- Language:English
-
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.
