Voronkova M A, Johnson B, Gandhi N, Koomen J M, Patrick M, Shanthi Bhupathi S, Wu V M, Elliott A, Vanderwalde A, Halmos B, Hazlehurst L A
West Virginia University Cancer Institute, Morgantown, WV, USA.
Caris Life Sciences, Phoenix, AZ, USA.
NPJ Precis Oncol. 2024 Nov 4;8(1):250. doi: 10.1038/s41698-024-00736-1.
We have identified endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) as a poor prognostic indicator in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (EGFR-NSCLC). In addition, comparison of high versus low ERO1A expression among cohorts of EGFR-NSCLC primary samples revealed that ERO1A expression correlated with increased expression of proteins that regulate secretion. Using the CPTAC proteomic data set in lung adenocarcinoma we found that high ERO1A protein expression correlated with both extracellular matrix and matrix modifying enzymes. In this report, we found that ablating ERO1A expression was a determinant of clonogenicity, tumor sphere formation, spheroid growth and growth in vivo, as well as response to Osimertinib. We validated that ERO1A-knockout EGFR-LUAD cell lines demonstrated a reduction in secretion of both laminin gamma 2 (LAMC2) and the collagen modifying enzyme lysyl oxidase-like 2 (LOXL2). Our work supports the role of ERO1A in modulating the tumor microenvironment that is likely to contribute to tumor progression.
我们已确定内质网氧化还原酶1α（ERO1A）是表皮生长因子受体（EGFR）突变的非小细胞肺癌（EGFR-NSCLC）的不良预后指标。此外，对EGFR-NSCLC原发性样本队列中ERO1A高表达与低表达的比较显示，ERO1A表达与调节分泌的蛋白质表达增加相关。利用肺腺癌的CPTAC蛋白质组数据集，我们发现ERO1A蛋白高表达与细胞外基质和基质修饰酶均相关。在本报告中，我们发现消除ERO1A表达是克隆形成、肿瘤球形成、球体生长和体内生长以及对奥希替尼反应的决定因素。我们验证了ERO1A基因敲除的EGFR-LUAD细胞系中，层粘连蛋白γ2（LAMC2）和胶原修饰酶赖氨酰氧化酶样2（LOXL2）的分泌均减少。我们的工作支持了ERO1A在调节肿瘤微环境中的作用，这可能有助于肿瘤进展。
