PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1
Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog...
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BMC
2024-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-04976-4 |
| _version_ | 1797266673743429632 |
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| author | Fuqiang Huang Jing Guo Na Zhao Mengjie Hou Xiaochen Gai Shuhui Yang Pei Cai Yanan Wang Qian Ma Qi Zhao Li Li Huayu Yang Yanling Jing Di Jin Zhongdong Hu Xiaojun Zha Hongyang Wang Yilei Mao Fangming Liu Hongbing Zhang |
| author_facet | Fuqiang Huang Jing Guo Na Zhao Mengjie Hou Xiaochen Gai Shuhui Yang Pei Cai Yanan Wang Qian Ma Qi Zhao Li Li Huayu Yang Yanling Jing Di Jin Zhongdong Hu Xiaojun Zha Hongyang Wang Yilei Mao Fangming Liu Hongbing Zhang |
| author_sort | Fuqiang Huang |
| collection | DOAJ |
| description | Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration. |
| first_indexed | 2024-04-25T01:04:26Z |
| format | Article |
| id | doaj.art-fcae3e2c4b5f427887e202af29fbad5f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-25T01:04:26Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-fcae3e2c4b5f427887e202af29fbad5f2024-03-10T12:20:58ZengBMCJournal of Translational Medicine1479-58762024-03-0122111110.1186/s12967-024-04976-4PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1Fuqiang Huang0Jing Guo1Na Zhao2Mengjie Hou3Xiaochen Gai4Shuhui Yang5Pei Cai6Yanan Wang7Qian Ma8Qi Zhao9Li Li10Huayu Yang11Yanling Jing12Di Jin13Zhongdong Hu14Xiaojun Zha15Hongyang Wang16Yilei Mao17Fangming Liu18Hongbing Zhang19State Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Cancer Stem Cell, Dalian Medical UniversityState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeInstitute of Cancer Stem Cell, Dalian Medical UniversityModern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese MedicineDepartment of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical UniversityInternational Co-Operation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical SciencesState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major Diseases, Haihe Laboratory of Cell Ecosystem, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.https://doi.org/10.1186/s12967-024-04976-4Hepatocellular carcinomaIntrahepatic cholangiocarcinomaHepatitis B virusPtenGP73 |
| spellingShingle | Fuqiang Huang Jing Guo Na Zhao Mengjie Hou Xiaochen Gai Shuhui Yang Pei Cai Yanan Wang Qian Ma Qi Zhao Li Li Huayu Yang Yanling Jing Di Jin Zhongdong Hu Xiaojun Zha Hongyang Wang Yilei Mao Fangming Liu Hongbing Zhang PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 Journal of Translational Medicine Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Hepatitis B virus Pten GP73 |
| title | PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 |
| title_full | PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 |
| title_fullStr | PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 |
| title_full_unstemmed | PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 |
| title_short | PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1 |
| title_sort | pten deficiency potentiates hbv associated liver cancer development through augmented gp73 golm1 |
| topic | Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Hepatitis B virus Pten GP73 |
| url | https://doi.org/10.1186/s12967-024-04976-4 |
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