Colon adenocarcinoma (COAD) is the commonest type of colorectal cancer with high morbidity and mortality worldwide. ETS variant 4 (ETV4) is a member of the ETS transcription factors and is frequently involved in the progression of many cancers. This study focused on the relevance of ETV4 to the progression of COAD. ETV4 was highly expressed in the collected COAD tissues and acquired cells and indicated advanced Dukes staging in patients. Knockdown of ETV4 in COAD cells weakened proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) activity of cells. The downstream genes of ETV4 were predicted, and a Gene Ontology (GO) analysis was conducted to identify the key molecule involved. ETV4 bound to the promoter sequence of HES1 and activated its transcription. Further overexpression of HES1 restored the malignant behaviors of COAD cells. HES1 was also found to promote phosphorylation of Stat3. Similar results were reproduced in vivo where downregulation of ETV4 blocked the growth of xenograft tumors in nude mice. This study demonstrated that ETV4 encourages malignant development of COAD through activating HES1 transcription and Stat3 phosphorylation. This study may offer novel insights into COAD therapy.

中文翻译：

---

ETV4转录激活HES1并促进Stat3磷酸化促进结肠腺癌的恶性行为

结肠腺癌 (COAD) 是全球最常见的结直肠癌类型，发病率和死亡率都很高。ETS 变体 4 (ETV4) 是 ETS 转录因子的成员，经常参与许多癌症的进展。本研究侧重于 ETV4 与 COAD 进展的相关性。ETV4 在收集的 COAD 组织和获得性细胞中高度表达，表明患者处于晚期 Dukes 分期。COAD 细胞中 ETV4 的敲低削弱了细胞的增殖、迁移、侵袭和上皮-间质转化 (EMT) 活性。预测了 ETV4 的下游基因，并进行了基因本体论 (GO) 分析以确定所涉及的关键分子。ETV4 与 HES1 的启动子序列结合并激活其转录。HES1的进一步过表达恢复了COAD细胞的恶性行为。还发现 HES1 可促进 Stat3 的磷酸化。在体内复制了类似的结果，其中 ETV4 的下调阻止了裸鼠异种移植肿瘤的生长。该研究表明，ETV4 通过激活 HES1 转录和 Stat3 磷酸化促进 COAD 的恶性发展。这项研究可能为 COAD 治疗提供新的见解。