Overexpressed COL3A1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-kB pathway

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-kB signaling pathway. These findings indicate that COL3A1 confers a poor prognosis and malignant phenotype by activating the NF-kB pathway in ESCC, potentially representing a novel biomarker and/or providing a new curative target for ESCC. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

In this study, it was found that COL3A1 is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and is associated with poor prognosis. Silencing COL3A1 inhibits tumor cell proliferation and migration, while overexpression of COL3A1 promotes tumor cell proliferation and migration. These findings highlight the important role of COL3A1 in ESCC and provide a new therapeutic target for the disease.