PDF(Pubmed)
Abstract：
In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.
MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.
MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.
摘要：
与发达国家的下降趋势相反，我国宫颈鳞癌的发病率和死亡率均有明显上升。为了提高患者的生存率和生活质量,迫切需要筛选和鉴定可靠的宫颈鳞癌生物标志物和候选药物靶点。在这项研究中,我们证明MUC1在宫颈肿瘤组织中的表达高于非肿瘤组织,MUC1高表达的宫颈鳞状细胞癌患者的总体生存率明显低于MUC1低表达的宫颈鳞状细胞癌患者，表明其对宫颈鳞状细胞癌的早期诊断的潜力。接下来,我们探讨了MUC1在宫颈鳞癌中的调控机制。MUC1可以通过ERK磷酸化上调ITGA2和ITGA3的表达,促进宫颈癌细胞的增殖和转移。进一步敲低ITGA2和ITGA3可显著抑制宫颈癌细胞的肿瘤发生。此外，我们设计了一种包含MUC1-siRNA和一种新型ERK抑制剂的体内联合用药方案,发现这些药物的联合用药在异种移植动物中取得了比单独使用MUC1更好的效果.总的来说,我们发现了一条新的调控途径,MUC1/ERK/ITGA2/3，在宫颈鳞状细胞癌中可能成为未来潜在的生物标志物和治疗靶点。
MUC1在宫颈鳞状细胞癌中过度表达。MUC1调节ERK磷酸化，并随后上调ITGA2和ITGA3的表达以促进宫颈鳞状细胞癌的肿瘤发生。与单独的MUC1相比,靶向MUC1和ERK的组合药物方案取得了更好的结果。
MUC1在宫颈鳞状细胞癌中过度表达。MUC1调节ERK磷酸化，并随后上调ITGA2和ITGA3的表达以促进宫颈鳞状细胞癌的肿瘤发生。与单独的MUC1相比,靶向MUC1和ERK的组合药物方案取得了更好的结果。
