Xu Yuanji, Zhu Kunshou, Chen Junqiang, Lin Liyan, Huang Zhengrong, Zhang Jiulong, Chen Yuanmei
Department of Radiation Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China.
Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China.
Carcinogenesis. 2021 Feb 25;42(2):254-262. doi: 10.1093/carcin/bgaa067.
SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.
SASS6编码人类SAS-6中心粒组装蛋白,对正确的中心体形成很重要。尽管在多种肿瘤类型中都存在中心体扩增,但此前仅在结肠癌中发现SASS6表达异常升高。此外,SASS6在食管鳞状细胞癌(ESCC)发病机制中的作用尚未阐明。本研究的目的是探讨SASS6在ESCC中的作用及机制。在本研究中,我们发现人类ESCC样本中SASS6的mRNA和蛋白水平升高。此外,SASS6蛋白表达与食管癌分期相关,并对ESCC患者的生存产生负面影响。此外,沉默SASS6可在体外抑制ESCC细胞的生长并促进其凋亡,在体内抑制异种移植肿瘤的形成。基因聚类和通路分析表明,SASS6调节p53信号通路。蛋白质印迹法显示,ESCC细胞中SASS6敲低后,CCND2、GADD45A和EIF4EBP1蛋白表达降低,TP53蛋白表达增加。因此,SASS6通过抑制p53信号通路促进食管癌的增殖。SASS6有潜力作为ESCC的新型肿瘤标志物和治疗靶点。