Yếu Tố Hoại Tử Khối U α Giảm Sự Hình Thành Autolysosome Phụ Thuộc SNAP29 Để Tăng Cường Mức Protein Prion Và Thúc Đẩy Sự Di Chuyển Của Tế Bào U

Virologica Sinica - Tập 36 - Trang 458-475 - 2020
Huan Li1,2,3, Ren Wang3, Ze Yu3, Run Shi3, Jie Zhang4, Shanshan Gao1, Ming Shao1, Shuzhong Cui3,5, Zhenxing Gao3, Jiang Xu4, Man-Sun Sy6, Chaoyang Li1,3
1Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
2University of Chinese Academy of Sciences, Beijing, China
3Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China
4Department of Stomatology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
5Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
6Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, USA

Tóm tắt

Yếu tố hoại tử khối u α (TNFα) được biết đến chủ yếu như một trung gian của sự viêm và miễn dịch, nhưng cũng đóng vai trò quan trọng trong sinh học khối u. Tuy nhiên, vai trò của TNFα trong sinh học khối u thì phức tạp và chưa được hiểu rõ hoàn toàn. Trong một dòng tế bào u ác tính người, M2, và một dòng tế bào carcinoma phổi, A549, TNFα tăng cường mức protein prion (PrP), và thúc đẩy sự di chuyển của tế bào u phụ thuộc vào PrP. Việc im lặng PRNP làm mất khả năng di chuyển tế bào u do TNFα tác động; hiện tượng này sẽ đảo ngược khi PRNP được đưa trở lại. Sự điều trị với TNFα kích hoạt tín hiệu yếu tố nhân kappa B (NF-κB), điều này giảm nhẹ quá trình tự thực bằng cách giảm sự biểu hiện của Forkhead Box P3 (FOXP3). Việc giảm biểu hiện FOXP3 làm giảm sự phiên mã của protein liên kết synaptosome 29 (SNAP29), protein này rất cần thiết trong việc hợp nhất autophagosome và lysosome tạo ra autolysosome. FOXP3 được xác nhận là một yếu tố phiên mã thật sự cho SNAP29 thông qua thử nghiệm gắn kết promoter. Vì vậy, việc kiểm soát lại SNAP29 trong các dòng tế bào này cũng làm tăng mức PrP, và thúc đẩy di chuyển tế bào u mà không cần điều trị với TNFα. Tuy nhiên, khi SNAP29 hoặc FOXP3 bị kiểm soát trong những tế bào này, chúng sẽ không còn phản ứng với TNFα. Do đó, việc giảm quá trình tự thực là cơ chế nền tảng mà qua đó sự biểu hiện của PrP được tăng cường, và sự di chuyển của tế bào u được nâng cao khi có điều trị TNFα. Sự phá vỡ trục tín hiệu TNFα-NF-κB-FOXP3-SNAP29 có thể cung cấp một phương pháp điều trị để giảm thiểu sự di chuyển tế bào u.

Từ khóa


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