RAGA prevents tumor immune evasion of LUAD by promoting CD47 lysosome degradation

作者全名："Zhang, Lian; Yu, Jing; Zheng, Mingyue; Zhen, Hui; Xie, Qingqiang; Zhang, Chundong; Zhou, Zhongjun; Jin, Guoxiang"

作者地址："[Zhang, Lian; Zheng, Mingyue; Zhen, Hui; Xie, Qingqiang; Jin, Guoxiang] Southern Med Univ, Guangdong Prov Peoples Hosp, Med Res Inst, Guangdong Acad Med Sci, Guangzhou 510080, Peoples R China; [Zhang, Lian; Zhou, Zhongjun] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China; [Zhang, Lian] Chongqing Med Univ, Coll Basic Med Sci, Chongqing 400016, Peoples R China; [Yu, Jing] Second Peoples Hosp Neijiang, Dept Surg Oncol, Neijiang 641000, Peoples R China; [Zhang, Chundong] Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Jin, Guoxiang] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Prov Geriatr Inst, Guangzhou 510080, Peoples R China"

通信作者："Jin, GX (通讯作者)，Southern Med Univ, Guangdong Prov Peoples Hosp, Med Res Inst, Guangdong Acad Med Sci, Guangzhou 510080, Peoples R China.; Zhou, ZJ (通讯作者)，Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China.; Jin, GX (通讯作者)，Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Prov Geriatr Inst, Guangzhou 510080, Peoples R China."

来源：COMMUNICATIONS BIOLOGY

ESI学科分类：　

WOS号：WOS:000955679400006

JCR分区：Q1

影响因子：5.9

年份：2023

卷号：6

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The lysosome protein RAGA interacts with and promotes lysosome localization and degradation of the macrophage-specific immune checkpoint protein CD47, with possible relevance to lung adenocarcinoma CD47 is a macrophage-specific immune checkpoint protein acting by inhibiting phagocytosis. However, the underlying mechanism maintaining CD47 protein stability in cancer is not clear. Here we show that CD47 undergoes degradation via endocytosis/lysosome pathway. The lysosome protein RAGA interacts with and promotes CD47 lysosome localization and degradation. Disruption of RAGA blocks CD47 degradation, leading to CD47 accumulation, high plasma membrane/intracellular CD47 expression ratio and reduced phagocytic clearance of cancer cells. RAGA deficiency promotes tumor growth due to the accumulation of CD47, which sensitizes the tumor to CD47 blockade. Clinical analysis shows that RAGA and CD47 proteins are negatively correlated in lung adenocarcinoma patient samples. High RAGA protein level is related to longer patient survival. In addition, RAGA(high)CD47(low) patients show the longest overall survival. Our study thereby not only reveals a mechanism by which RAGA regulates CD47 lysosome degradation, but also suggests RAGA is a potential diagnostic biomarker of lung adenocarcinoma."

基金机构："National Natural Science Foundation of China [81773040, 81972774]; Science and Technology Innovation Project of Chongqing Science and Technology Commission [cstc2018jcyj-yszxX0011]; Guangdong Provincial People's Hospital, High-level Hospital Construction Project [KJ012021074, KJ012019517]"

基金资助正文："AcknowledgementsWe thank all lab members for their critical reading, valuable comments, and suggestions. This study was supported by the National Natural Science Foundation of China (81773040 and 81972774); Science and Technology Innovation Project of Chongqing Science and Technology Commission (cstc2018jcyj-yszxX0011); and Guangdong Provincial People's Hospital, High-level Hospital Construction Project (KJ012021074 and KJ012019517)."