Serine protease inhibitor kazal-type 6 inhibits tumorigenesis of human hepatocellular carcinoma cells via its extracellular action
| Autor: | Jinjiang Huang, Hongyu Wu, Xinchuan Dai, Kuikui Ge, Yuqiang Xu, Hairong Lu, Qingshan Huang, Jiang Zhong, Guodong Li, Meigang Gu, Wei Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular tumor suppressor MAP Kinase Signaling System proliferation Down-Regulation Apoptosis medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Cell Movement SPINK6 Cell Line Tumor medicine Animals Humans HCC Cell Proliferation Serine protease biology business.industry Serine Peptidase Inhibitors Kazal Type Liver Neoplasms Hep G2 Cells medicine.disease invasion Phenotype Virology digestive system diseases Oncolytic virus Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Hepatocellular carcinoma biology.protein Carcinogenesis business Neoplasm Transplantation Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Kuikui Ge 1, * , Jinjiang Huang 1, * , Wei Wang 1 , Meigang Gu 2 , Xinchuan Dai 1 , Yuqiang Xu 1 , Hongyu Wu 1, 3 , Guodong Li 3 , Hairong Lu 3 , Jiang Zhong 1 , Qingshan Huang 1 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China 2 Laboratory of Virology and Infectious Disease Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10065, USA 3 Shanghai High-Tech United Bio-Technological R&D Co., Ltd, Shanghai 201206, China * These authors contributed equally to this work Correspondence to: Qingshan Huang, email: qshuang@fudan.edu.cn Keywords: SPINK6, HCC, tumor suppressor, invasion, proliferation Received: April 11, 2016 Accepted: December 12, 2016 Published: December 16, 2016 ABSTRACT Hepatocellular carcinoma (HCC) causes significant medical burdens worldwide. Diagnosis, especially in the early stages, is still challenging. Therapeutic options are limited and often ineffective. Although several risk factors have been known important for development of HCC, the molecular basis of the process is rather complex and has not been fully understood. We have found that a subpopulation of HCC cells which are resistant to oncolytic parvovirus H1 superinfection highly express serine protease inhibitor Kazal-type 6 (SPINK6). This protein is specifically reduced in all HCC cell lines and tissues we analyzed. When upregulated, SPINK6 could suppress the malignant phenotypes of the HCC cells in several in vitro models. The putative tumor suppression role of SPINK6 is, however, independent of its protease inhibitory activity. To suppress the malignancy of HCC cells, SPINK6 has to be secreted to trigger signals which regulate an intracellular signaling molecule, ERK1/2, as well as a series of downstream factors involved in cell cycle progression, apoptosis and migration. Our study supports that SPINK6 is an important tumor suppressor in liver, and further investigations may help develop more effective diagnostic and therapeutic approaches. |
| Databáze: | OpenAIRE |
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