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<p>Gastric cancer is among the most prevalent gastrointestinal tumors, with liver metastasis significantly worsening patient outcomes. While hepatic stellate cell activation is crucial in hepatocellular carcinoma progression and liver metastasis, its role in gastric cancer liver metastasis is not well understood. In this study, we identified Suprabasin (SBSN) as a key oncogene driving gastric cancer liver metastasis. SBSN was upregulated in gastric cancer tissues and further elevated in liver metastasis, correlating with poor prognosis. Mechanistically, SBSN promoted proliferation, migration, and invasion of gastric cancer cells by activating the STAT3 signaling pathway, as shown in vitro and in vivo. Using a co-culture model of gastric cancer cells and hepatic stellate cell line LX-2, we found that increased SBSN expression in gastric cancer cells triggered EGF secretion, activating LX-2 cells through the EGF/EGFR axis. Activated LX-2 cells then secreted CCL2, initiating the CCL2/CCR2/JAK2 signaling pathway in gastric cancer cells, facilitating their migration to the liver and promoting colonization and growth. Our findings highlight the prognostic significance of SBSN in gastric cancer and liver metastasis, suggesting it as a potential biomarker for disease progression. The SBSN-mediated EGF/EGFR and CCL2/CCR2/JAK2 signaling axes are critical for LX-2 activation and gastric cancer cell migration, offering a rationale for targeting SBSN in treating gastric cancer liver metastasis.</p>

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Suprabasin promotes gastric cancer liver metastasis via hepatic stellate cells-mediated EGF/CCL2/JAK2 intercellular signaling pathways

  • 期刊论文

  • 发表日期：

    2025年4月3日

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  • Difeng Li,
  • Zhiqing Gao,
  • Zhuojun Zhang,
  • Han Chen,
  • Ruiming Tang,
  • Lihuan Zhou,
  • Yingmin Ye,
  • Jiaqian Lin,
  • Ping Zhou,
  • Chanjuan Wang,
  • Xiaoli Feng,
  • Yaoming He,
  • Zijie Meng,
  • Mingzhu Zheng,
  • Wenjie Lu,
  • Zhengfu Feng,
  • Lan Wang,
  • Yuanyuan Pei,
  • Jianan Yang,
  • Tianyu Tao,
  • Xin Zhang,
  • Lili Jiang

摘要

Gastric cancer is among the most prevalent gastrointestinal tumors, with liver metastasis significantly worsening patient outcomes. While hepatic stellate cell activation is crucial in hepatocellular carcinoma progression and liver metastasis, its role in gastric cancer liver metastasis is not well understood. In this study, we identified Suprabasin (SBSN) as a key oncogene driving gastric cancer liver metastasis. SBSN was upregulated in gastric cancer tissues and further elevated in liver metastasis, correlating with poor prognosis. Mechanistically, SBSN promoted proliferation, migration, and invasion of gastric cancer cells by activating the STAT3 signaling pathway, as shown in vitro and in vivo. Using a co-culture model of gastric cancer cells and hepatic stellate cell line LX-2, we found that increased SBSN expression in gastric cancer cells triggered EGF secretion, activating LX-2 cells through the EGF/EGFR axis. Activated LX-2 cells then secreted CCL2, initiating the CCL2/CCR2/JAK2 signaling pathway in gastric cancer cells, facilitating their migration to the liver and promoting colonization and growth. Our findings highlight the prognostic significance of SBSN in gastric cancer and liver metastasis, suggesting it as a potential biomarker for disease progression. The SBSN-mediated EGF/EGFR and CCL2/CCR2/JAK2 signaling axes are critical for LX-2 activation and gastric cancer cell migration, offering a rationale for targeting SBSN in treating gastric cancer liver metastasis.