Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Br J Cancer. 2023 Apr;128(8):1478-1490. doi: 10.1038/s41416-023-02150-z. Epub 2023 Feb 9.
Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Finding effective prognostic markers and therapeutic targets is of great significance for controlling metastasis and invasion clinically.
The open copy-number aberrations and gene expression datasets were analysed, and the data of 102 LUAD patients was used for further validation. The cell proliferation, colony formation, migration, invasion assays and mice tumor models were used to detect the function of SEC61G. The epidermal growth factor receptor (EGFR) pathway was also detected to find the mechanism of Sec61γ.
Based on the open datasets, we found that the high level of SEC61G mRNA may drive LUAD metastasis. Furthermore, the overexpression of Sec61γ protein was significantly associated with poor prognosis and greater tumor cell proliferation and metastasis. The SEC61G knockdown could inhibit the EGFR pathway, including STAT3, AKT and PI3K, which can be reversed by Sec61γ overexpression and epithelial growth factor (EGF) supplement.
Sec61γ promoted the proliferation, metastasis, and invasion of LUAD through EGFR pathways. Sec61γ might be a potential target for the treatment of LUAD metastases.
肺腺癌（LUAD）是全球最常见的恶性肿瘤之一。寻找有效的预后标志物和治疗靶点对于临床控制转移和侵袭具有重要意义。
分析了公开的拷贝数畸变和基因表达数据集，并对 102 名 LUAD 患者的数据进行了进一步验证。通过细胞增殖、集落形成、迁移、侵袭试验和小鼠肿瘤模型来检测 SEC61G 的功能。还检测了表皮生长因子受体（EGFR）途径，以寻找 Sec61γ的作用机制。
基于公开数据集，我们发现 SEC61G mRNA 水平高可能会驱动 LUAD 转移。此外，Sec61γ蛋白的过表达与不良预后以及更大的肿瘤细胞增殖和转移显著相关。SEC61G 的敲低可以抑制 EGFR 途径，包括 STAT3、AKT 和 PI3K，而 Sec61γ 的过表达和表皮生长因子（EGF）补充可以逆转这种抑制作用。
Sec61γ 通过 EGFR 途径促进 LUAD 的增殖、转移和侵袭。Sec61γ 可能是治疗 LUAD 转移的潜在靶点。
