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<p>Owing to the lack of effective therapeutic strategies, peritoneal metastasis of metastatic and recurrent gastric cancers is associated with poor prognosis. Our previous study showed that galectin-4 suppression attenuated the peritoneal metastasis of malignant gastric cancer cells in a mouse model; however, the underlying mechanisms are unclear. Therefore, we aimed to elucidate the role of galectin-4 in signal transduction by identifying interacting molecules and the relationship to glycans. Antibody array analysis and proximity ligation assays revealed a close association between galectin-4 and multiple receptor tyrosine kinases (RTKs), including c-MET and EGFR. In galectin-4 knockout (KO) cells, tyrosine phosphorylation of RTKs proximal to galectin-4 was markedly reduced. Enhanced tyrosine phosphorylation promoted cell surface exposure and colocalization of galectin-4 and tyrosine-phosphorylated (PY) proteins. Surface plasmon resonance and inhibition assays further revealed that galectin-4 binds to tyrosine-phosphorylated molecules via its carbohydrate recognition domain. Consistently, overexpression of B3GALT5, a β1-3-galactosyltransferase, altered the localization of PY proteins and galectin-4, suggesting competitive regulation of galectin-4 binding by glycosylation and tyrosine phosphorylation. Notably, galectin-4 KO cells exhibited reduced c-MET surface expression. Collectively, these findings suggest that galectin-4 plays a critical role in maintaining the expression and activation of multiple signaling molecules involved in peritoneal metastasis.</p>

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Galectin-4 contributes to the maintenance of expression and activation of multiple receptor-type kinases involved in peritoneal metastasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Hiroko Ideo,
  • Miwa Umebayashi,
  • Yoshio Takada,
  • Akiko Tsuchida

摘要

Owing to the lack of effective therapeutic strategies, peritoneal metastasis of metastatic and recurrent gastric cancers is associated with poor prognosis. Our previous study showed that galectin-4 suppression attenuated the peritoneal metastasis of malignant gastric cancer cells in a mouse model; however, the underlying mechanisms are unclear. Therefore, we aimed to elucidate the role of galectin-4 in signal transduction by identifying interacting molecules and the relationship to glycans. Antibody array analysis and proximity ligation assays revealed a close association between galectin-4 and multiple receptor tyrosine kinases (RTKs), including c-MET and EGFR. In galectin-4 knockout (KO) cells, tyrosine phosphorylation of RTKs proximal to galectin-4 was markedly reduced. Enhanced tyrosine phosphorylation promoted cell surface exposure and colocalization of galectin-4 and tyrosine-phosphorylated (PY) proteins. Surface plasmon resonance and inhibition assays further revealed that galectin-4 binds to tyrosine-phosphorylated molecules via its carbohydrate recognition domain. Consistently, overexpression of B3GALT5, a β1-3-galactosyltransferase, altered the localization of PY proteins and galectin-4, suggesting competitive regulation of galectin-4 binding by glycosylation and tyrosine phosphorylation. Notably, galectin-4 KO cells exhibited reduced c-MET surface expression. Collectively, these findings suggest that galectin-4 plays a critical role in maintaining the expression and activation of multiple signaling molecules involved in peritoneal metastasis.