PDF(Pubmed)
Abstract：
UNASSIGNED: Recurrence and metastasis are the major obstacles affecting the therapeutic efficacy and clinical outcomes for patients with esophageal carcinoma (ESCA). Secreted phosphoprotein 1 (SPP1) is considered as a hub gene in ESCA and is negatively associated with disease-free survival (DFS) in ESCA. However, the exact roles and underlying mechanisms remain elusive. This study aims to examine the roles of SPP1 on ESCA, and elucidate the potential mechanisms.
UNASSIGNED: Bioinformatics were used to analyze the expression of SPP1 in ESCA tissues, and its relations with clinicopathological characteristics and clinical prognosis in patients with ESCA based on The Cancer Genome Atlas (TCGA) dataset. Loss-of-function was conducted to examine the roles of SPP1 on malignant behaviors of ESCA cells by cell counting kit-8 (CCK8), plate clone, wound healing, and transwell assays. Gene set enrichment analysis (GSEA) was conducted to screen the pathways associated with SPP1 in ESCA. Then, the enriched pathway and the underlying mechanism were elucidated by western blotting, cell adhesion, and cell spreading assays. Lastly, Y15 [a specific inhibitor of focal adhesion kinase (FAK)] was used to examine its potential to inhibit tumor growth in ESCA cells.
UNASSIGNED: SPP1 was upregulated in ESCA tissues compared to the adjacent nontumorous tissues, which was closely associated with clinical stage, lymph node metastasis, histological subtype, and p53 mutation. A high expression of SPP1 indicated a poor clinical prognosis in patients with ESCA. The knockdown of SPP1 inhibited cell proliferative, migratory, and invasive capacities in ESCA cells. GSEA indicated that the focal adhesion pathway was closely related with SPP1 in ESCA. Further studies confirmed that the knockdown of SPP1 suppressed cell adhesion ability and reduced the expression of p-FAK and p-Erk in ESCA cells. In addition, Y15 inhibited FAK autophosphorylation and dramatically inhibited cell proliferation, migration, and invasion in ESCA cells.
UNASSIGNED: SPP1 promotes tumor progression in ESCA by activating FAK/Erk pathway, and FAK is a potential therapeutic target to overcome tumor recurrence and metastasis of ESCA.
UNASSIGNED: Bioinformatics were used to analyze the expression of SPP1 in ESCA tissues, and its relations with clinicopathological characteristics and clinical prognosis in patients with ESCA based on The Cancer Genome Atlas (TCGA) dataset. Loss-of-function was conducted to examine the roles of SPP1 on malignant behaviors of ESCA cells by cell counting kit-8 (CCK8), plate clone, wound healing, and transwell assays. Gene set enrichment analysis (GSEA) was conducted to screen the pathways associated with SPP1 in ESCA. Then, the enriched pathway and the underlying mechanism were elucidated by western blotting, cell adhesion, and cell spreading assays. Lastly, Y15 [a specific inhibitor of focal adhesion kinase (FAK)] was used to examine its potential to inhibit tumor growth in ESCA cells.
UNASSIGNED: SPP1 was upregulated in ESCA tissues compared to the adjacent nontumorous tissues, which was closely associated with clinical stage, lymph node metastasis, histological subtype, and p53 mutation. A high expression of SPP1 indicated a poor clinical prognosis in patients with ESCA. The knockdown of SPP1 inhibited cell proliferative, migratory, and invasive capacities in ESCA cells. GSEA indicated that the focal adhesion pathway was closely related with SPP1 in ESCA. Further studies confirmed that the knockdown of SPP1 suppressed cell adhesion ability and reduced the expression of p-FAK and p-Erk in ESCA cells. In addition, Y15 inhibited FAK autophosphorylation and dramatically inhibited cell proliferation, migration, and invasion in ESCA cells.
UNASSIGNED: SPP1 promotes tumor progression in ESCA by activating FAK/Erk pathway, and FAK is a potential therapeutic target to overcome tumor recurrence and metastasis of ESCA.
摘要：
■复发和转移是影响食管癌（ESCA）患者治疗效果和临床结局的主要障碍。分泌磷蛋白1（SPP1）被认为是ESCA中的hub基因，与ESCA中的无病生存（DFS）呈负相关。然而,确切的作用和潜在的机制仍然难以捉摸。本研究旨在考察SPP1在ESCA中的作用，并阐明潜在的机制。
■生物信息学用于分析ESCA组织中SPP1的表达，基于癌症基因组图谱（TCGA）数据集，及其与ESCA患者临床病理特征和临床预后的关系。用细胞计数试剂盒8(CCK8)检测SPP1在ESCA细胞恶性行为中的作用,平板克隆,伤口愈合，和transwell分析。进行基因集富集分析（GSEA）以筛选与ESCA中SPP1相关的途径。然后，通过蛋白质印迹阐明了富集途径和潜在机制，细胞粘附，和细胞铺展试验。最后,Y15[粘着斑激酶（FAK）的特异性抑制剂]用于检查其抑制ESCA细胞中肿瘤生长的潜力。
■与邻近的非肿瘤组织相比，ESCA组织中的SPP1上调，这与临床分期密切相关，淋巴结转移,组织学亚型，p53突变。SPP1的高表达表明ESCA患者的临床预后不良。SPP1敲低抑制细胞增殖,迁徙,和ESCA细胞的侵袭能力。GSEA表明ESCA中粘着斑通路与SPP1密切相关。进一步研究证实，SPP1的敲低抑制了细胞粘附能力，并降低了ESCA细胞中p-FAK和p-Erk的表达。此外,Y15抑制FAK自磷酸化并显著抑制细胞增殖,迁移,和ESCA细胞的侵袭。
■SPP1通过激活FAK/Erk通路促进ESCA肿瘤进展，FAK是克服ESCA肿瘤复发和转移的潜在治疗靶点。
■生物信息学用于分析ESCA组织中SPP1的表达，基于癌症基因组图谱（TCGA）数据集，及其与ESCA患者临床病理特征和临床预后的关系。用细胞计数试剂盒8(CCK8)检测SPP1在ESCA细胞恶性行为中的作用,平板克隆,伤口愈合，和transwell分析。进行基因集富集分析（GSEA）以筛选与ESCA中SPP1相关的途径。然后，通过蛋白质印迹阐明了富集途径和潜在机制，细胞粘附，和细胞铺展试验。最后,Y15[粘着斑激酶（FAK）的特异性抑制剂]用于检查其抑制ESCA细胞中肿瘤生长的潜力。
■与邻近的非肿瘤组织相比，ESCA组织中的SPP1上调，这与临床分期密切相关，淋巴结转移,组织学亚型，p53突变。SPP1的高表达表明ESCA患者的临床预后不良。SPP1敲低抑制细胞增殖,迁徙,和ESCA细胞的侵袭能力。GSEA表明ESCA中粘着斑通路与SPP1密切相关。进一步研究证实，SPP1的敲低抑制了细胞粘附能力，并降低了ESCA细胞中p-FAK和p-Erk的表达。此外,Y15抑制FAK自磷酸化并显著抑制细胞增殖,迁移,和ESCA细胞的侵袭。
■SPP1通过激活FAK/Erk通路促进ESCA肿瘤进展，FAK是克服ESCA肿瘤复发和转移的潜在治疗靶点。
