MTHFD1L confers a poor prognosis and malignant phenotype in esophageal squamous cell carcinoma by activating the ERK5 signaling pathway.
MTHFD1L confers a poor prognosis and malignant phenotype in esophageal squamous cell carcinoma by activating the ERK5 signaling pathway.
复制标题
DOI：
10.1016/j.yexcr.2023.113584
复制
发表时间：
2023-03
影响因子：
3.7
通讯作者：
Jianfeng Zhou;Yushang Yang;Jiahan Cheng;S. Luan;X. Xiao;Xiaokun Li;Pinhao Fang;Yimin Gu;Q. Shang;Han-lu Zhang;Longqi Chen;Xiaoxi Zeng;Yong Yuan
中科院分区：
文献类型：
--
作者：
Jianfeng Zhou;Yushang Yang;Jiahan Cheng;S. Luan;X. Xiao;Xiaokun Li;Pinhao Fang;Yimin Gu;Q. Shang;Han-lu Zhang;Longqi Chen;Xiaoxi Zeng;Yong Yuan
MTHFD1L是叶酸代谢的关键酶，在肿瘤中的研究报道较少。在这项研究中，我们探讨MTHFD1L在食管鳞状细胞癌（ESCC）的致瘤性中的作用。ESCC组织微阵列（TMAs）包含109例患者的177个样本，用于评估MTHFD1L表达，使用免疫组化分析确定，是否是ESCC患者的预后指标。通过体外伤口愈合、Transwell和三维球体侵袭实验以及体内肺转移小鼠模型研究MTHFD1L在ESCC细胞迁移和侵袭中的功能。采用mRNA芯片技术和免疫途径分析（IPA）技术对MTHFD1L下游基因进行分析。MTHFD1L在食管鳞癌组织中的高表达与食管鳞癌的分化程度和预后密切相关。这些表型分析表明，MTHFD1L在体内和体外显著促进ESCC细胞的存活和转移。进一步详细的分子机制分析表明，MTHFD1L通过上调ERK 5信号通路驱动ESCC进展。这些发现揭示了MTHFD1L通过激活ERK 5信号通路与ESCC的侵袭性表型正相关，提示MTHFD1L是ESCC的新生物标志物和潜在的分子治疗靶点。
MTHFD1L, a key enzyme of folate metabolism, is seldom reported in cancer. In this study, we investigate the role of MTHFD1L in the tumorigenicity of esophageal squamous cell carcinoma (ESCC). ESCC tissue microarrays (TMAs) containing 177 samples from 109 patients were utilized to evaluate whether MTHFD1L expression, determined using immunohistochemical analysis, is a prognostic indicator for ESCC patients. The function of MTHFD1L in the migration and invasion of ESCC cells was studied with wound healing, Transwell, and three-dimensional spheroid invasion assays in vitro and a lung metastasis mouse model in vivo. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MTHFD1L. Elevated expression of MTHFD1L in ESCC tissues was significantly associated with poor differentiation and prognosis. These phenotypic assays revealed that MTHFD1L significantly promote the viability and metastasis of ESCC cell in vivo and in vitro. Further detailed analyses of the molecular mechanism demonstrated that the ESCC progression driven by MTHFD1L was through up-regulation ERK5 signaling pathways. These findings reveal that MTHFD1L is positively associated with the aggressive phenotype of ESCC by activating ERK5 signaling pathways, suggesting that MTHFD1L is a new biomarker and a potential molecular therapeutic target for ESCC.