The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism

作者全名："Zhu, Ke-Gan; Yang, Jiayu; Zhu, Yuehong; Zhu, Qihang; Pan, Wen; Deng, Siyu; He, Yi; Zuo, Duo; Wang, Peiyun; Han, Yueting; Zhang, Hai-Yang"

作者地址："[Zhu, Ke-Gan; Yang, Jiayu; Zhu, Yuehong; Zhu, Qihang; Pan, Wen; He, Yi; Zuo, Duo; Wang, Peiyun; Han, Yueting; Zhang, Hai-Yang] Tianjin Med Univ, Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc,Key Lab Canc Prevent &, Tianjin 300060, Peoples R China; [Deng, Siyu; Zhang, Hai-Yang] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China"

通信作者："Zhang, HY (通讯作者)，Tianjin Med Univ, Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc,Key Lab Canc Prevent &, Tianjin 300060, Peoples R China.; Zhang, HY (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing 400016, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001095595000001

JCR分区：Q1

影响因子：9

年份：2023

卷号：14

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Lymph node metastasis (LNM) is the prominent route of gastric cancer dissemination, and usually leads to tumor progression and a dismal prognosis of gastric cancer. Although exosomal lncRNAs have been reported to be involved in tumor development, whether secreted lncRNAs can encode peptides in recipient cells remains unknown. Here, we identified an exosomal lncRNA (lncAKR1C2) that was clinically correlated with lymph node metastasis in gastric cancer in a VEGFC-independent manner. Exo-lncAKR1C2 secreted from gastric cancer cells was demonstrated to enhance tube formation and migration of lymphatic endothelial cells, and facilitate lymphangiogenesis and lymphatic metastasis in vivo. By comparing the metabolic characteristics of LN metastases and primary focuses, we found that LN metastases of gastric cancer displayed higher lipid metabolic activity. Moreover, exo-lncAKR1C2 encodes a microprotein (pep-AKR1C2) in lymphatic endothelial cells and promotes CPT1A expression by regulating YAP phosphorylation, leading to enhanced fatty acid oxidation (FAO) and ATP production. These findings highlight a novel mechanism of LNM and suggest that the microprotein encoded by exosomal lncAKR1C2 serves as a therapeutic target for advanced gastric cancer."

基金机构："National Natural Science Foundation of China [82173125, 81974374]; Science & Technology Development Fund of Tianjin Education Commission for Higher Education [2020KJ127]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (Nos. 82173125, 81974374) and The Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2020KJ127). The funders had no role in the study design, the data collection and analysis, the interpretation of thedata, the writing of the report, and the decision to submit this article for publication"