Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways
Abstract Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization...
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doaj-ad15022ad276415a9ef743e08fb87fa42021-05-02T11:05:31ZengNature Publishing GroupCell Death and Disease2041-48892021-04-0112511410.1038/s41419-021-03711-xSerum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathwaysXi Chen0Weijie Ma1Ye Yao2Qi Zhang3Jinghua Li4Xiaoling Wu5Chengjie Mei6Xiang Jiang7Yiran Chen8Ganggang Wang9Kunlei Wang10Yingyi Liu11Yonghua Guo12Zhisu Liu13Yufeng Yuan14Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of General Medicine, Renmin Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan UniversityAbstract Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC.https://doi.org/10.1038/s41419-021-03711-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xi Chen Weijie Ma Ye Yao Qi Zhang Jinghua Li Xiaoling Wu Chengjie Mei Xiang Jiang Yiran Chen Ganggang Wang Kunlei Wang Yingyi Liu Yonghua Guo Zhisu Liu Yufeng Yuan |
spellingShingle |
Xi Chen Weijie Ma Ye Yao Qi Zhang Jinghua Li Xiaoling Wu Chengjie Mei Xiang Jiang Yiran Chen Ganggang Wang Kunlei Wang Yingyi Liu Yonghua Guo Zhisu Liu Yufeng Yuan Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways Cell Death and Disease |
author_facet |
Xi Chen Weijie Ma Ye Yao Qi Zhang Jinghua Li Xiaoling Wu Chengjie Mei Xiang Jiang Yiran Chen Ganggang Wang Kunlei Wang Yingyi Liu Yonghua Guo Zhisu Liu Yufeng Yuan |
author_sort |
Xi Chen |
title |
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways |
title_short |
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways |
title_full |
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways |
title_fullStr |
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways |
title_full_unstemmed |
Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways |
title_sort |
serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ask1-jnk/p38 mapk pathways |
publisher |
Nature Publishing Group |
series |
Cell Death and Disease |
issn |
2041-4889 |
publishDate |
2021-04-01 |
description |
Abstract Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC. |
url |
https://doi.org/10.1038/s41419-021-03711-x |
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