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

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

  • Neoplasia. 2024 Dec:58:101067. doi: 10.1016/j.neo.2024.101067.
Huiwen Luan 1,  Ting Wang 2,  Fangmin Li 1,  Shuang Sun 3,  Zhenbo Wang 4,  Xinyu Zhao 1,  Feng Kong 5,  Tao Hu 6,  Yifan Liu 1,  Juan Zhang 1,  Xiaoli Liu 1,  Hongying Wang 1,  Xianhui Meng 1,  Chunling Li 1,  Jiashen Zhang 7,  Shuhao Ji 1,  Lijun Hui 1,  Siman Nie 1,  Yaopeng Wang 8,  Zunling Li 9
Affiliations

Affiliations

  • 1 Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumor Immunotherapy Research Innovation Team, Binzhou Medical University, Yantai, Shandong 264003, PR China.
  • 2 Department of Pathology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong 264099, PR China.
  • 3 Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumor Immunotherapy Research Innovation Team, Binzhou Medical University, Yantai, Shandong 264003, PR China; Department of Laboratory Medicine, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong 264099, PR China.
  • 4 Department of Binzhou Medical University Hospital, Binzhou, Shandong 256600, PR China.
  • 5 Shandong Institute of Clinical Medicine, Shandong Provincial Hospital, Jinan, Shandong 250021, PR China.
  • 6 Department of Thoracic Surgery, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong 264099, PR China.
  • 7 Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumor Immunotherapy Research Innovation Team, Binzhou Medical University, Yantai, Shandong 264003, PR China; Department of Biochemistry and Molecular Biology, School of Life Sciences, Shandong Agricultural University, Taian, Shandong 271018, PR China.
  • 8 Department of Thoracic Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong 266011, PR China. Electronic address: qdwyaopeng@qdslyy.freeqiye.com.
  • 9 Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumor Immunotherapy Research Innovation Team, Binzhou Medical University, Yantai, Shandong 264003, PR China. Electronic address: lizunling@bzmc.edu.cn.
PMID: 39383800 DOI: 10.1016/j.neo.2024.101067
Abstract

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

Anti-IGSF9; EMT; IGSF9; Invasion; Metastasis.

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