Unknown

Dataset Information

0

Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.


ABSTRACT: One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression.

SUBMITTER: Wu JR 

PROVIDER: S-EPMC4741710 | BioStudies | 2015-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6684519 | BioStudies
2016-01-01 | S-EPMC5087290 | BioStudies
2015-01-01 | S-EPMC4301873 | BioStudies
1000-01-01 | S-EPMC4905458 | BioStudies
2001-01-01 | S-EPMC87257 | BioStudies
2015-01-01 | S-EPMC4351203 | BioStudies
2017-01-01 | S-EPMC5440344 | BioStudies
2008-01-01 | S-EPMC2574998 | BioStudies
1000-01-01 | S-EPMC4896053 | BioStudies
2009-01-01 | S-EPMC3427732 | BioStudies