FBXW7 inhibits the progression of ESCC by directly inhibiting the stemness of tumor cells.
FBXW7 inhibits the progression of ESCC by directly inhibiting the stemness of tumor cells.
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DOI：
10.4149/neo_2023_230104n8
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发表时间：
2023-11
期刊：
影响因子：
3
通讯作者：
Y. Bi;Yanfang Yang;Yong Zhang;Caixia Cheng;Peisen Tang;Heng Xiao;Fajia Yuan;Weiwei Wu
中科院分区：
文献类型：
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作者：
Y. Bi;Yanfang Yang;Yong Zhang;Caixia Cheng;Peisen Tang;Heng Xiao;Fajia Yuan;Weiwei Wu
含有7的F-box和WD重复结构域（FBXW7）是一种与食管鳞状细胞癌（ESCC）相关的原始高频突变基因。本研究旨在确定FBXW7在ESCC发展中的临床价值和分子机制。结合TCGA数据分析FBXW7在ESCC中的临床意义。研究了FBXW7对ESCC细胞增殖、集落形成、迁移侵袭、血管生成和凋亡的影响。采用PCR-array、球形成实验和实时定量聚合酶链反应（qPCR）技术探讨FBXW7的作用机制。FBXW7是ESCC中显著突变的基因。它是ESCC患者独立且潜在的生存预测指标。此外，FBXW7过表达显著抑制ESCC细胞增殖、迁移、侵袭、血管生成，促进细胞凋亡。PCR结果显示，FBXW7过表达导致血管生成、细胞衰老、DNA损伤与修复相关基因表达发生显著变化。球体形成实验和qPCR显示FBXW7与ESCC干细胞形成相关。我们的研究结果表明FBXW7可能通过抑制ESCC肿瘤干细胞形成、调节肿瘤血管生成、细胞衰老、DNA损伤和修复而发挥肿瘤抑制作用。
F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of genes expression associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.