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Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of FOXO1

Yang Yang1, Xiaodi Yan2, YueYuan Chen3

  • 1Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province 226001, China.

Current Pharmaceutical Design
|February 12, 2024
PubMed
Abstract

Insights

Inhibition of Fucosyltransferase4 (FUT4) activates Forkhead box O1 (FOXO1), reducing osteosarcoma cell proliferation, invasion, and migration. This suggests FUT4 inhibition is a potential therapeutic strategy for osteosarcoma by targeting the Wnt/β-catenin pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Fucosyltransferase4 (FUT4) inhibition activates Forkhead box O1 (FOXO1), inducing cancer cell apoptosis.
  • The precise mechanism of FUT4 and FOXO1 in osteosarcoma remains unclear.

Purpose of the Study:

  • To investigate the biological role of the FUT4-FOXO1 interaction in osteosarcoma progression.
  • To determine if FUT4 inhibition impacts osteosarcoma cell proliferation, migration, invasion, and apoptosis.

Main Methods:

  • Utilized in vitro assays with human osteoblast and osteosarcoma cell lines.
  • Assessed FUT4 and FOXO1 expression via qRT-PCR and Western blot.
  • Evaluated osteosarcoma cell proliferation, migration, invasion, and apoptosis using CCK-8, colony, EDU, wound healing, Transwell, and TUNEL assays.
  • Investigated the Wnt/β-catenin signaling pathway and related protein markers.

Main Results:

  • Osteosarcoma cells exhibited higher FUT4 expression compared to osteoblasts.
  • FUT4 inhibition significantly suppressed osteosarcoma cell proliferation, invasion, and migration.
  • Inhibition of FUT4 led to increased osteosarcoma cell apoptosis.
  • FUT4 inhibition blocked the Wnt/β-catenin pathway by upregulating FOXO1 expression.

Conclusions:

  • Osteosarcoma cells overexpress FUT4.
  • FUT4 inhibition targets FOXO1 activation, impacting the Wnt/β-catenin pathway and reducing osteosarcoma cell viability.
  • Targeting FUT4 offers a potential therapeutic strategy for osteosarcoma treatment.
Keywords:
FOXO1FUT4apoptosis.migrationosteosarcoma cellsproliferation

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