Overexpressed COL3A1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-κB pathway.
Overexpressed COL3A1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-κB pathway.
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DOI：
10.1016/j.bbrc.2022.05.029
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发表时间：
2022-05
影响因子：
3.1
通讯作者：
Jianfeng Zhou;Yu-Shang Yang;Han-lu Zhang;S. Luan;X. Xiao;Xiaokun Li;Pinhao Fang;Q. Shang;Longqi Chen;Xiaoxi Zeng;Yong Yuan
中科院分区：
文献类型：
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作者：
Jianfeng Zhou;Yu-Shang Yang;Han-lu Zhang;S. Luan;X. Xiao;Xiaokun Li;Pinhao Fang;Q. Shang;Longqi Chen;Xiaoxi Zeng;Yong Yuan
Alpha-1 Ⅲ型胶原蛋白 (COL3A1) 编码胶原蛋白 alpha-1(Ⅲ) 链，这是一种存在于可伸展结缔组织中的纤维状胶原蛋白。很少有研究报道其在致瘤性中的作用。在本研究中，我们发现与正常食管鳞状上皮细胞相比，食管鳞状细胞癌 (ESCC) 细胞中 COL3A1 蛋白和 mRNA 表达水平显着上调 (P < 0.05)。对 114 份石蜡包埋存档的 ESCC 组织进行的免疫组织化学 (IHC) 分析表明，COL3A1 表达与术后 T 分期呈正相关。单变量和多变量分析表明，COL3A1 表达是整个队列总体生存的独立不良预后因素。沉默COL3A1抑制ESCC细胞的增殖、迁移和侵袭，而过表达COL3A1则促进ESCC细胞的增殖、迁移和侵袭。此外，COL3A1表达的下调还抑制了皮下异种移植小鼠模型中ESCC的生长，并抑制了肺转移小鼠模型中ESCC的转移。此外，我们证明COL3A1对ESCC细胞的促瘤作用与NF-κB信号通路的激活有关。这些发现表明，COL3A1 通过激活 ESCC 中的 NF-κB 通路而导致不良预后和恶性表型，可能代表一种新的生物标志物和/或为 ESCC 提供新的治疗靶点。
Alpha-1 Type Ⅲ Collagen (COL3A1) encodes the Collagen alpha-1(Ⅲ) chain, which is a fibrillar collagen that exists in extensile connective tissues. Few studies have reported its role in tumorigenicity. In the present study, we identified that COL3A1 protein and mRNA expression levels were considerably up-regulated in esophageal squamous cell carcinoma (ESCC) cells in comparison with normal esophageal squamous epithelial cells (P < 0.05). Immunohistochemical (IHC) analysis of 114 paraffin-embedded archived ESCC tissues demonstrated that COL3A1 expression was positively correlated with the postoperative T stage. Univariate and multivariable analysis demonstrated that COL3A1 expression was an independent poor prognostic factor for overall survival in the whole cohort. Silencing COL3A1 inhibited, while overexpressing COL3A1 promoted, the proliferation, migration, and invasion of ESCC cells. Furthermore, down-regulation of COL3A1 expression also suppressed the growth of ESCC in subcutaneous xenograft mouse models and inhibited ESCC metastasis in lung metastasis mouse models. In addition, we proved that the tumor-promoting effect of COL3A1 on ESCC cells was related to the activation of NF-κB signaling pathway. These findings indicate that COL3A1 confers a poor prognosis and malignant phenotype by activating the NF-κB pathway in ESCC, potentially representing a novel biomarker and/or providing a new curative target for ESCC.