Lu Hao, Xu Wan-Lin, Wu Yi-Fan, Yang Wen-Jun, Liu Sheng-Wen
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Dent Sci. 2023 Oct;18(4):1651-1662. doi: 10.1016/j.jds.2023.01.035. Epub 2023 Feb 10.
BACKGROUND/PURPOSE: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored.
Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC and .
We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells . MUC1 knockdown significantly inhibited tumor growth , and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway.
Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.
背景/目的:唾液腺癌(SGC)是头颈部常见的恶性肿瘤,预后较差。据报道,黏蛋白1(MUC1)与癌症的发生发展有关。然而,MUC1是否促进SGC的进展仍有待探索。
采用免疫组织化学分析方法探讨MUC1在SGC组织中的表达水平。进行细胞增殖、集落形成、伤口愈合、Transwell和异种移植试验,以检测MUC1对SGC的影响。
我们发现SGC组织中MUC1的表达水平显著上调,且MUC1的表达水平与SGC的淋巴结转移及TNM分期显著相关。进一步研究表明,敲低MUC1可显著抑制SGC细胞的生长、集落形成、迁移和侵袭能力,而过表达MUC1则具有促进作用。敲低MUC1可显著抑制肿瘤生长,反之亦然。更重要的是,我们发现MUC1通过调节表皮生长因子受体(EGFR)信号通路促进SGC细胞的恶性表型。
我们的结果表明,MUC1通过介导EGFR信号通路促进SGC的发展,这突出了MUC1/EGFR在SGC中的潜在治疗靶点。