Scholarlink

<p>Esophageal squamous cell carcinoma (ESCC) is a common digestive tract tumor influenced by tumor-associated macrophages (TAMs), which promote progression through M2 polarization. Analysis of GSE75241 showed that PRSS23 was significantly upregulated in ESCC samples compared with non-tumors (<i>n</i> = 15). Its high expression corresponded to poorer overall survival in macrophages-enriched ESCC patients (Log-rank <i>p</i> = 0.04). Furthermore, PRSS23 expression was elevated in ESCC tissues compared with normal controls (<i>n</i> = 12) and positively correlated with CD206 expression (<i>n</i> = 14), suggesting a potential role for PRSS23 in ESCC progression <i>via</i> the regulation of TAMs. PRSS23 knockdown suppressed the malignant phenotype of ESCC cells, including proliferation, migration, and invasion. In vivo, nude mice bearing PRSS23-silenced ESCC cells developed smaller tumors with fewer M2-type TAMs. Consistently, PRSS23 knockdown impaired macrophage chemotaxis and M2 polarization in co-culture with ESCC cells. Zinc finger E-box binding homeobox 1 (ZEB1) was predicted as an upstream regulator of PRSS23. Overexpression of ZEB1 increased the transcriptional activity of the PRSS23 promoter (–1110 ~ + 15&#xa0;bp) by 2.55-fold compared to the vector control, confirming ZEB1 as a positive transcriptional regulator. Notably, PRSS23 knockdown rescued the promoting effects of ZEB1 overexpression on ESCC cells and macrophage M2 polarization. Further transcriptomic analysis of macrophages suggested that PRSS23 mediates M2 polarization through the Wnt/β-catenin pathway. Accordingly, PRSS23 knockdown inhibited both Wnt/β-catenin signaling and M2 polarization in co-cultured macrophages, effects that were reversed by the Wnt/β-catenin agonist SKL2001. Collectively, our findings showed that the ZEB1/PRSS23 axis promotes ESCC progression by driving M2 polarization of TAMs, offering a potential therapeutic target for ESCC treatment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PRSS23 functions downstream of ZEB1 to promote esophageal squamous cell carcinoma progression by driving M2 polarization of tumor associated macrophages

  • 期刊论文

  • 发表日期：

    2026年4月10日

查看全文
  • Wei Chen,
  • Chanjuan Chen,
  • Zhongyun Hu,
  • Fanfan Li,
  • Yao Peng,
  • Mingjun Zhang

摘要

Esophageal squamous cell carcinoma (ESCC) is a common digestive tract tumor influenced by tumor-associated macrophages (TAMs), which promote progression through M2 polarization. Analysis of GSE75241 showed that PRSS23 was significantly upregulated in ESCC samples compared with non-tumors (n = 15). Its high expression corresponded to poorer overall survival in macrophages-enriched ESCC patients (Log-rank p = 0.04). Furthermore, PRSS23 expression was elevated in ESCC tissues compared with normal controls (n = 12) and positively correlated with CD206 expression (n = 14), suggesting a potential role for PRSS23 in ESCC progression via the regulation of TAMs. PRSS23 knockdown suppressed the malignant phenotype of ESCC cells, including proliferation, migration, and invasion. In vivo, nude mice bearing PRSS23-silenced ESCC cells developed smaller tumors with fewer M2-type TAMs. Consistently, PRSS23 knockdown impaired macrophage chemotaxis and M2 polarization in co-culture with ESCC cells. Zinc finger E-box binding homeobox 1 (ZEB1) was predicted as an upstream regulator of PRSS23. Overexpression of ZEB1 increased the transcriptional activity of the PRSS23 promoter (–1110 ~ + 15 bp) by 2.55-fold compared to the vector control, confirming ZEB1 as a positive transcriptional regulator. Notably, PRSS23 knockdown rescued the promoting effects of ZEB1 overexpression on ESCC cells and macrophage M2 polarization. Further transcriptomic analysis of macrophages suggested that PRSS23 mediates M2 polarization through the Wnt/β-catenin pathway. Accordingly, PRSS23 knockdown inhibited both Wnt/β-catenin signaling and M2 polarization in co-cultured macrophages, effects that were reversed by the Wnt/β-catenin agonist SKL2001. Collectively, our findings showed that the ZEB1/PRSS23 axis promotes ESCC progression by driving M2 polarization of TAMs, offering a potential therapeutic target for ESCC treatment.