| Autor: |
Xudong Wan, Yuantao Liu, Yiman Peng, Jian Wang, Shu‐mei Yan, Lu Zhang, Wanchun Wu, Lei Zhao, Xuelan Chen, Kexin Ren, Haicheng Long, Yiling Luo, Qin Yan, Lele Zhang, Dengzhi Lei, Pengpeng Liu, Shujun Li, Lihui Liu, Linjie Guo, Jiajia Du, Mengsha Zhang, Siqi Dai, Yi Yang, Hongyu Liu, Nianyong Chen, Jinxin Bei, Lin Feng, Yu Liu, Mu‐sheng Zeng, Chong Chen, Qian Zhong |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 11, Iss 36, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202403161 |
| Popis: |
Abstract Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein‐Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV‐ (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC‐associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene‐edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV‐coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV‐ and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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