Cheeloo College of Medicine, Qilu Hospital, ShanDong University, China.
The Third Affiliated Hospital of BaoTou Medical College, Mongolia, China.
FEBS Open Bio. 2021 May;11(5):1497-1503. doi: 10.1002/2211-5463.13105. Epub 2021 Mar 28.
More than 40 000 patients worldwide die from esophageal cancer annually. The 5-year survival rate of patients is only ~ 15-20%, and thus, there is an ongoing need to improve diagnosis and treatment of esophageal cancer. Breast cancer type 1 susceptibility protein (BRCA1)-associated protein (BAP1) is a marker of poor prognosis in several cancers, including uveal melanoma, renal cell carcinoma, cholangiocarcinoma, non-small cell lung cancer, and colorectal cancer. BAP1 mutations are early and rare events in esophageal carcinoma, but the involvement of BAP1 in progression of esophageal carcinoma is unclear. Here, we report that cell proliferation and migration were significantly enhanced in esophageal carcinoma ECA109 cells overexpressing BAP1, while they were diminished upon BAP1 knockdown. In addition, the expression of Krüppel-like factor 5 (KLF5), CyclinD1, and FGF-BP1 was increased by BAP1 overexpression and decreased by BAP1 knockdown. Our data suggest that BAP1 promotes cell proliferation and migration, and enhances the expression of KLF5 and its downstream genes, including CyclinD1 and FGF-BP1, in the esophageal carcinoma cell line ECA109.
全世界每年有超过 40,000 人死于食管癌。患者的 5 年生存率仅约为 15-20%，因此，需要不断改进食管癌的诊断和治疗方法。乳腺癌 1 型易感蛋白 (BRCA1) 相关蛋白 (BAP1) 是包括葡萄膜黑色素瘤、肾细胞癌、胆管癌、非小细胞肺癌和结直肠癌在内的几种癌症的预后不良标志物。BAP1 突变是食管癌的早期和罕见事件，但 BAP1 在食管癌进展中的作用尚不清楚。在这里，我们报告在过表达 BAP1 的食管癌 ECA109 细胞中，细胞增殖和迁移显著增强，而在敲低 BAP1 后则减少。此外，BAP1 的过表达增加了 Krüppel 样因子 5 (KLF5)、CyclinD1 和 FGF-BP1 的表达，而 BAP1 的敲低则降低了它们的表达。我们的数据表明，BAP1 促进了食管癌细胞系 ECA109 中的细胞增殖和迁移，并增强了 KLF5 及其下游基因，包括 CyclinD1 和 FGF-BP1 的表达。
