AKT的磷酸化通过类溶氨酸氧化酶2活化PI3K / AKT信号通路,促进食道鳞癌的增殖,侵袭和转移。
Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma.
发表日期:2023 Mar 30
作者:
Zhiqin Fan, Yingmin Liu, Xinya Liu, Wei Nian, Xiaotong Huang, Qianqian Yang, Songyu Hou, Fei Chen
来源:
GENES & DEVELOPMENT
摘要:
食管鳞癌(ESCC)是胃肠道常见且具有侵袭性的恶性肿瘤,治疗选择有限。本研究筛查了在ESCC中的关键基因LOXL2,并解释了它促进ESCC进展的分子机制。应用免疫组化染色检测LOXL2在ESCC组织和癌旁组织中的表达水平,采用CCK-8和Transwell实验评估LOXL2敲降和过表达对ESCC细胞增殖、凋亡、迁移和侵袭能力的影响。高通量测序分析筛查LOXL2促进ESCC进展的分子机制。采用Western blot和qRT-PCR确定相关标志物的表达水平。LOXL2在ESCC中呈阳性表达,与不良预后高度相关。沉默LOXL2显著抑制了ESCC细胞的增殖、迁移和侵袭能力,而过表达则呈相反的表型。高通量测序表明,LOXL2相关的差异表达基因在PI3K / AKT信号通路中高度富集。体外细胞实验证实,沉默LOXL2显著降低了PI3K、p-AKTThr308和p-AKTSer473基因和蛋白水平的表达,而过表达则增加了所有三个基因和蛋白水平的表达,而AKT基因和蛋白水平的表达差异不显著。本研究发现,LOXL2通过AKT的磷酸化可能调节PI3K / AKT信号通路,并对ESCC细胞产生原肿瘤效应。LOXL2可能是ESCC的关键临床预警生物标志物或治疗靶点。© 2023.作者( s)。
Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC.Immunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers.LOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different.This study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC.© 2023. The Author(s).