The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.
The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.
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外泌体LNCAKR1C2编码的微蛋白通过调节脂肪酸代谢来促进胃癌淋巴结转移。
DOI：
10.1038/s41419-023-06220-1
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发表时间：
2023-10-30
影响因子：
9
通讯作者：
Zhang, Hai-Yang
中科院分区：
文献类型：
--
作者：
Zhu, Ke-Gan;Yang, Jiayu;Zhu, Yuehong;Zhu, Qihang;Pan, Wen;Deng, Siyu;He, Yi;Zuo, Duo;Wang, Peiyun;Han, Yueting;Zhang, Hai-Yang
淋巴结转移（LNM）是胃癌转移的主要途径，常导致胃癌的进展和预后不良。虽然已报道外泌体lncRNA参与肿瘤的发展，但分泌的lncRNA是否能在受体细胞中编码肽仍是未知的。在这里，我们确定了一个外泌体lncRNA（lncAKR 1C 2），在临床上与胃癌淋巴结转移的VEGF无关的方式。胃癌细胞分泌的exo-lncAKR 1C 2在体内被证明能促进淋巴管内皮细胞的管形成和迁移，并促进淋巴管生成和淋巴转移。通过比较淋巴结转移灶与原发灶的代谢特点，发现胃癌淋巴结转移灶具有较高的脂代谢活性。此外，外切-lncAKR 1C 2编码淋巴管内皮细胞中的微蛋白（pep-AKR 1C 2），并通过调节雅普磷酸化促进CPT 1A表达，导致脂肪酸氧化（FAO）和ATP产生增强。这些发现突出了LNM的新机制，并表明由外泌体lncAKR 1C 2编码的微蛋白可作为晚期胃癌的治疗靶点。
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.
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影响因子：
5.7
作者：
通讯作者：
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LNMAT1 通过 CCL2 依赖性巨噬细胞募集促进膀胱癌淋巴转移
影响因子：
16.6
作者：
Chen C;He W;Huang J;Wang B;Li H;Cai Q;Su F;Bi J;Liu H;Zhang B;Jiang N;Zhong G;Zhao Y;Dong W;Lin T
通讯作者：
Lin T
DOI：
10.1186/s13046-022-02505-z
发表时间：
2022-10-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
通讯作者：
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影响因子：
158.5
作者：
Morton, Donald L.;Thompson, John F.;Wang, He-Jing
通讯作者：
Wang, He-Jing
影响因子：
9
作者：
Rault-Petit, Berenice;Do Cao, Christine;Walter, Thomas
通讯作者：
Walter, Thomas