Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou 310058, China.
Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China.
Cells. 2022 Aug 1;11(15):2363. doi: 10.3390/cells11152363.
The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples and samples from the TCGA and GEO databases and found that ENO2 upregulation in CRC samples was negatively associated with prognosis. By knocking down and overexpressing ENO2, we found that ENO2 promoted CRC cell migration and invasion, which is dependent on its interaction with the long noncoding RNA (lncRNA) CYTOR, but did not depend on glycolysis regulation. Furthermore, CYTOR mediated ENO2 binding to large tumor suppressor 1 (LATS1) and competitively inhibited the phosphorylation of Yes-associated protein 1 (YAP1), which ultimately triggered epithelial-mesenchymal transition (EMT). Collectively, these findings highlight the molecular mechanism of the ENO2-CYTOR interaction, and ENO2 could be considered a potential therapeutic target for CRC.
糖酵解酶烯醇化酶 2（ENO2）在许多类型的癌症中失调。然而，ENO2 在结直肠癌（CRC）转移中的作用和详细的分子机制仍不清楚。在这里，我们对 184 个局部 CRC 样本和 TCGA 和 GEO 数据库中的样本进行了ENO2 表达的全面分析，发现 CRC 样本中 ENO2 的上调与预后呈负相关。通过敲低和过表达 ENO2，我们发现 ENO2 促进 CRC 细胞迁移和侵袭，这依赖于其与长链非编码 RNA（lncRNA）CYTOR 的相互作用，但不依赖于糖酵解调节。此外，CYTOR 介导 ENO2 与大肿瘤抑制因子 1（LATS1）结合，并竞争性抑制 Yes 相关蛋白 1（YAP1）的磷酸化，最终引发上皮-间充质转化（EMT）。总之，这些发现强调了 ENO2-CYTOR 相互作用的分子机制，ENO2 可以被认为是 CRC 的一个潜在治疗靶点。
