ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1
| العنوان: | ORP4L is a prerequisite for the induction of T-cell leukemogenesis associated with human T-cell leukemia virus 1 |
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| المؤلفون: | Daoguang Yan, Yu Huang, Wenbin Zhong, Xiuye Cao, Guoping Pan, Meng-Yang Xu, Qun Niu, Qing Yi, Xiaoqin Feng, Mingchuan Li |
| المصدر: | Blood. 139:1052-1065 |
| بيانات النشر: | American Society of Hematology, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Receptors, Steroid, Carcinogenesis, T-Lymphocytes, T cell, Immunology, Apoptosis, Biochemistry, Virus, Mice, hemic and lymphatic diseases, Tumor Cells, Cultured, medicine, Pi, Animals, Humans, Leukemia-Lymphoma, Adult T-Cell, Protein kinase B, Cell Proliferation, Human T-lymphotropic virus 1, Hyperactivation, Gene Expression Regulation, Leukemic, Chemistry, Mechanism (biology), Gene Products, tax, Cell Biology, Hematology, Prognosis, medicine.disease, HTLV-I Infections, Xenograft Model Antitumor Assays, Human T cell leukemia virus, Leukemia, medicine.anatomical_structure, Cancer research |
| الوصف: | Human T-cell leukemia virus 1 (HTLV-1) causes adult T-cell leukemia (ATL), but the mechanism underlying its initiation remains elusive. In this study, ORP4L was expressed in ATL cells but not in normal T-cells. ORP4L ablation completely blocked T-cell leukemogenesis induced by the HTLV-1 oncoprotein Tax in mice, whereas engineering ORP4L expression in T-cells resulted in T-cell leukemia in mice, suggesting the oncogenic properties and prerequisite of ORP4L promote the initiation of T-cell leukemogenesis. For molecular insight, we found that loss of miR-31 caused by HTLV-1 induced ORP4L expression in T-cells. ORP4L interacts with PI3Kδ to promote PI(3,4,5)P3 generation, contributing to AKT hyperactivation; NF-κB–dependent, p53 inactivation-induced pro-oncogene expression; and T-cell leukemogenesis. Consistently, ORP4L ablation eliminates human ATL cells in patient-derived xenograft ATL models. These results reveal a plausible mechanism of T-cell deterioration by HTLV-1 that can be therapeutically targeted. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d51da57051e6de7c93638950da36898fTest https://doi.org/10.1182/blood.2021013579Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d51da57051e6de7c93638950da36898f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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