分支链酮酸脱氢酶激酶（BCKDK）是支链氨基酸（BCAA）代谢的速率限制酶。在过去的六年里，BCKDK已被用作一种激酶来促进肿瘤的增殖和转移。肾细胞癌（RCC）是一种高血管化的肿瘤。高度的血管化促进了肿瘤的转移。我们的目标是探讨BCKDK和RCC转移之间的关系及其具体机制。在我们的研究中，BCKDK在肾透明细胞癌中高度表达，并促进透明细胞肾细胞癌（ccRCC）的迁移。ccRCC细胞释放的外泌体能够促进血管通透性和血管生成，尤其是当ccRCC细胞中过表达BCKDK时。BCKDK还可以增强ccRCC细胞和衍生外泌体中miR-125a-5p的表达，从而降低下游靶蛋白VE-cadherin的水平，削弱粘附连接的表达，增加血管通透性，并促进人脐静脉内皮细胞（HUVECs）的血管生成。新的BCKDK/外泌体-miR-125a-5p/VE-cadherin轴调控了ccRCC细胞与HUVECs之间的细胞间通讯。BCKDK在肾癌转移中发挥着关键作用，可能被用作转移性ccRCC的分子标记，并可能成为ccRCC临床抗血管疗法的潜在靶点。 © 2023 The Authors. 由澳大利亚约翰·威立出版社出版的癌症科学代表日本癌症协会。

Branched-chain keto-acid dehydrogenase kinase (BCKDK) is the rate-limiting enzyme of branched-chain amino acid (BCAA) metabolism. In the last six years, BCKDK has been used as a kinase to promote tumor proliferation and metastasis. Renal cell carcinoma (RCC) is a highly vascularized tumor. A high degree of vascularization promotes tumor metastasis. Our objective is to explore the relationship between BCKDK and RCC metastasis and its specific mechanism. In our study, BCKDK is highly expressed in renal clear cell carcinoma and promotes the migration of clear cell renal cell carcinoma (ccRCC). Exosomes from ccRCC cells can promote vascular permeability and angiogenesis, especially when BCKDK is overexpressed in ccRCC cells. BCKDK can also augment the miR-125a-5p expression in ccRCC cells and derived exosomes, thereby decreasing the downstream target protein VE-cadherin level, weakening adhesion junction expression, increasing vascular permeability, and promoting angiogenesis in HUVECs. The novel BCKDK/Exosome-miR-125a-5p/VE-cadherin axis regulates intercellular communication between ccRCC cells and HUVECs. BCKDK plays a critical role in renal cancer metastasis, may be used as a molecular marker of metastatic ccRCC, and even may become a potential target of clinical anti-vascular therapy for ccRCC.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.