LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma
Summary: Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this stu...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223008313 |
| _version_ | 1797827773795926016 |
|---|---|
| author | Jianping Liao Jiahong Wang Yu Xu Yong Wu Meifeng Wang Qiudong Zhao Xiaodan Tan Yan Meng Lixin Wei Aimin Huang |
| author_facet | Jianping Liao Jiahong Wang Yu Xu Yong Wu Meifeng Wang Qiudong Zhao Xiaodan Tan Yan Meng Lixin Wei Aimin Huang |
| author_sort | Jianping Liao |
| collection | DOAJ |
| description | Summary: Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this study, we identified that lysosome-associated protein transmembrane-4β (LAPTM4B) was significantly overexpressed in stem-like tumor cell populations with multidirectional differentiation potential at the single cell level, and verified that LAPTM4B was closely related to stemness of HCC using in vitro and in vivo experiments. Mechanistically, elevated LAPTM4B suppresses Yes-associated protein (YAP) phosphorylation and ubiquitination degradation. In turn, stabilized YAP localizes to the nucleus and binds to cAMP responsive element binding protein-1 (CREB1), which promotes transcription of LAPTM4B. Overall, our findings suggest that LAPTM4B forms a positive feedback loop with YAP, which maintains the stemness of HCC tumor cells and leads to an unfavorable prognosis for HCC patients. |
| first_indexed | 2024-04-09T12:53:44Z |
| format | Article |
| id | doaj.art-64916cafd73d4ea298aeb9c1bd2ed092 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T12:53:44Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-64916cafd73d4ea298aeb9c1bd2ed0922023-05-14T04:29:23ZengElsevieriScience2589-00422023-06-01266106754LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinomaJianping Liao0Jiahong Wang1Yu Xu2Yong Wu3Meifeng Wang4Qiudong Zhao5Xiaodan Tan6Yan Meng7Lixin Wei8Aimin Huang9Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, ChinaDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, ChinaDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, ChinaDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, ChinaDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, ChinaTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, 225 Changhai Road, Shanghai 200438, ChinaDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, ChinaTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, 225 Changhai Road, Shanghai 200438, China; Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai 200072, China; Corresponding authorTumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, 225 Changhai Road, Shanghai 200438, China; Corresponding authorDepartment of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, Fujian 350004, China; Corresponding authorSummary: Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this study, we identified that lysosome-associated protein transmembrane-4β (LAPTM4B) was significantly overexpressed in stem-like tumor cell populations with multidirectional differentiation potential at the single cell level, and verified that LAPTM4B was closely related to stemness of HCC using in vitro and in vivo experiments. Mechanistically, elevated LAPTM4B suppresses Yes-associated protein (YAP) phosphorylation and ubiquitination degradation. In turn, stabilized YAP localizes to the nucleus and binds to cAMP responsive element binding protein-1 (CREB1), which promotes transcription of LAPTM4B. Overall, our findings suggest that LAPTM4B forms a positive feedback loop with YAP, which maintains the stemness of HCC tumor cells and leads to an unfavorable prognosis for HCC patients.http://www.sciencedirect.com/science/article/pii/S2589004223008313Cell biologyStem cells researchCancer systems biologyCancer |
| spellingShingle | Jianping Liao Jiahong Wang Yu Xu Yong Wu Meifeng Wang Qiudong Zhao Xiaodan Tan Yan Meng Lixin Wei Aimin Huang LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma iScience Cell biology Stem cells research Cancer systems biology Cancer |
| title | LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| title_full | LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| title_fullStr | LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| title_full_unstemmed | LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| title_short | LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| title_sort | laptm4b yap loop feedback amplification enhances the stemness of hepatocellular carcinoma |
| topic | Cell biology Stem cells research Cancer systems biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223008313 |
| work_keys_str_mv | AT jianpingliao laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT jiahongwang laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT yuxu laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT yongwu laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT meifengwang laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT qiudongzhao laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT xiaodantan laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT yanmeng laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT lixinwei laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma AT aiminhuang laptm4byaploopfeedbackamplificationenhancesthestemnessofhepatocellularcarcinoma |