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<p>Gastric cancer (GC) is a leading cause of cancer-related mortality characterized by aggressive metastasis and limited therapeutic options. Kin of IRRE-like protein 1 (KIRREL1) is an emerging cell surface protein whose specific oncogenic role in GC remains largely unknown. Therefore, the intention of this study was to comprehensively investigate the clinical relevance, biological functions, and underlying molecular mechanisms of KIRREL1 in GC progression. The expression and prognostic value of KIRREL1 were evaluated using data from The Cancer Genome Atlas (TCGA) and in vitro experiments. Gain- and loss-of-function studies were performed in GC cell lines to assess the effects of KIRREL1 on proliferation, 5-FU chemosensitivity, migration, and invasion. Western blotting was used to examine the regulation of epithelial-mesenchymal transition (EMT) markers. KIRREL1 was significantly upregulated in GC tissues and cell lines, and its high expression was strongly correlated with poor progression-free, disease-specific, and overall survival in patients. Functionally, KIRREL1 overexpression promoted GC cell proliferation, migration, and invasion, whereas its knockdown had the opposite effects. Furthermore, KIRREL1 knockdown sensitized GC cells to 5-FU treatment. Mechanistically, KIRREL1 was found to positively regulate the expression of the key EMT markers Vimentin, MMP2, and MMP9. Our findings identify KIRREL1 as a novel oncogene that actively promotes GC proliferation, 5-FU chemoresistance, and metastasis via the EMT pathway. Importantly, this establishes KIRREL1 as both a robust prognostic biomarker and a targetable driver of malignancy. Future clinical perspectives should explore the development of specific KIRREL1 inhibitors to overcome chemoresistance and suppress metastatic dissemination.</p>

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KIRREL1 is a novel prognostic biomarker that promotes malignancy in gastric cancer via activation of the epithelial-mesenchymal transition pathway

  • 期刊论文

  • 发表日期：

    2026年5月19日

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  • Huohua Lv,
  • Jun Liu,
  • Lufei Jiang,
  • ZhiWen Nie,
  • Yaoxin Wang

摘要

Gastric cancer (GC) is a leading cause of cancer-related mortality characterized by aggressive metastasis and limited therapeutic options. Kin of IRRE-like protein 1 (KIRREL1) is an emerging cell surface protein whose specific oncogenic role in GC remains largely unknown. Therefore, the intention of this study was to comprehensively investigate the clinical relevance, biological functions, and underlying molecular mechanisms of KIRREL1 in GC progression. The expression and prognostic value of KIRREL1 were evaluated using data from The Cancer Genome Atlas (TCGA) and in vitro experiments. Gain- and loss-of-function studies were performed in GC cell lines to assess the effects of KIRREL1 on proliferation, 5-FU chemosensitivity, migration, and invasion. Western blotting was used to examine the regulation of epithelial-mesenchymal transition (EMT) markers. KIRREL1 was significantly upregulated in GC tissues and cell lines, and its high expression was strongly correlated with poor progression-free, disease-specific, and overall survival in patients. Functionally, KIRREL1 overexpression promoted GC cell proliferation, migration, and invasion, whereas its knockdown had the opposite effects. Furthermore, KIRREL1 knockdown sensitized GC cells to 5-FU treatment. Mechanistically, KIRREL1 was found to positively regulate the expression of the key EMT markers Vimentin, MMP2, and MMP9. Our findings identify KIRREL1 as a novel oncogene that actively promotes GC proliferation, 5-FU chemoresistance, and metastasis via the EMT pathway. Importantly, this establishes KIRREL1 as both a robust prognostic biomarker and a targetable driver of malignancy. Future clinical perspectives should explore the development of specific KIRREL1 inhibitors to overcome chemoresistance and suppress metastatic dissemination.