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

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 t...

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Autores principales: Wu, Jia-Ru, Hu, Chi-Tan, You, Ren-In, Pan, Siou-Mei, Cheng, Chuan-Chu, Lee, Ming-Che, Wu, Chao-Chuan, Chang, Yao-Jen, Lin, Shu-Chuan, Chen, Chang-Shan, Lin, Teng-Yi, Wu, Wen-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741710/
https://www.ncbi.nlm.nih.gov/pubmed/26416447
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author Wu, Jia-Ru
Hu, Chi-Tan
You, Ren-In
Pan, Siou-Mei
Cheng, Chuan-Chu
Lee, Ming-Che
Wu, Chao-Chuan
Chang, Yao-Jen
Lin, Shu-Chuan
Chen, Chang-Shan
Lin, Teng-Yi
Wu, Wen-Sheng
author_facet Wu, Jia-Ru
Hu, Chi-Tan
You, Ren-In
Pan, Siou-Mei
Cheng, Chuan-Chu
Lee, Ming-Che
Wu, Chao-Chuan
Chang, Yao-Jen
Lin, Shu-Chuan
Chen, Chang-Shan
Lin, Teng-Yi
Wu, Wen-Sheng
author_sort Wu, Jia-Ru
collection PubMed
description 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.
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spelling pubmed-47417102016-03-11 Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression Wu, Jia-Ru Hu, Chi-Tan You, Ren-In Pan, Siou-Mei Cheng, Chuan-Chu Lee, Ming-Che Wu, Chao-Chuan Chang, Yao-Jen Lin, Shu-Chuan Chen, Chang-Shan Lin, Teng-Yi Wu, Wen-Sheng Oncotarget Research Paper 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. Impact Journals LLC 2015-09-22 /pmc/articles/PMC4741710/ /pubmed/26416447 Text en Copyright: © 2015 Wu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wu, Jia-Ru
Hu, Chi-Tan
You, Ren-In
Pan, Siou-Mei
Cheng, Chuan-Chu
Lee, Ming-Che
Wu, Chao-Chuan
Chang, Yao-Jen
Lin, Shu-Chuan
Chen, Chang-Shan
Lin, Teng-Yi
Wu, Wen-Sheng
Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title_full Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title_fullStr Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title_full_unstemmed Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title_short Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
title_sort hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741710/
https://www.ncbi.nlm.nih.gov/pubmed/26416447
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