Li Zhenyuan, Lu Tailiang, Chen Zhian, Yu Xiang, Wang Lingzhi, Shen Guodong, Huang Huilin, Li Zhenhao, Ren Yingxin, Guo Weihong, Hu Yanfeng
Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, the First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, P.R. China.
iScience. 2023 Jul 13;26(8):107346. doi: 10.1016/j.isci.2023.107346. eCollection 2023 Aug 18.
Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFβ1 expression and activates the TGFβ1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.
大多数早期胃癌（GC）患者通常无淋巴结（LN）转移，而LN转移出现在晚期。然而，有一些患者在早期出现LN转移，而在晚期无LN转移。为了探究其中更深层次的分子机制，我们收集了伴有和不伴有LN转移的早期和晚期GC的临床样本以及转移性淋巴结。在此，我们鉴定出一个关键靶点HOXA11，其在GC组织中上调且与淋巴转移密切相关。HOXA11转录调控TGFβ1表达并激活TGFβ1/Smad2通路，这不仅促进上皮-间质转化（EMT）发展，还诱导VEGF-C分泌和淋巴管生成。这些发现为HOXA11调节的肿瘤淋巴转移提供了一个合理的机制，并表明HOXA11可能代表LN转移性胃癌临床干预的一个潜在治疗靶点。
