Neoplasia: An International Journal for Oncology Research (Dec 2024)

IGSF9 promotes tumor invasion and metastasis through GSK-3β/β-catenin mediated EMT in lung cancer

  • Huiwen Luan,
  • Ting Wang,
  • Fangmin Li,
  • Shuang Sun,
  • Zhenbo Wang,
  • Xinyu Zhao,
  • Feng Kong,
  • Tao Hu,
  • Yifan Liu,
  • Juan Zhang,
  • Xiaoli Liu,
  • Hongying Wang,
  • Xianhui Meng,
  • Chunling Li,
  • Jiashen Zhang,
  • Shuhao Ji,
  • Lijun Hui,
  • Siman Nie,
  • Yaopeng Wang,
  • Zunling Li

Journal volume & issue
Vol. 58
p. 101067

Abstract

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We previously reported that immunoglobulin superfamily member 9 (IGSF9) as a tumor specific immune checkpoint promoted the tumor immune escape, however, as an adhesion molecule, whether IGSF9 promotes tumor invasion and metastasis has not been reported. Here, the full length, the intracellular domain (ID) not extracellular domain (ECD) of IGSF9 could alter tumor cell morphology from a flat and polygonal shape to elongated strips, suggesting that IGSF9 signal pathway has the potential to mediate epithelial-to-mesenchymal transition (EMT). Real-time PCR and western blotting also showed that the mesenchymal markers were significantly up-regulated, and the epithelial markers were significantly down-regulated in IGSF9 and IGSF9-ID groups. Meanwhile, immunofluorescence showed that β-catenin was clearly translocated into the nucleus in IGSF9 and IGSF9-ID groups. The in vitro and in vivo data showed that IGSF9, IGSF9-ID and ECD could promote tumor invasion and metastasis. Mechanistically, IGSF9-ID could recruit GSK-3β to result in the accumulation and nuclear translocation of β-catenin to trigger EMT. Anti-IGSF9 could significantly inhibit the invasion and metastasis, and IGSF9 is an effective candidate for lung cancer therapy.

Keywords