NKD2 as a Mediator of IFIX Antioncogene-Induced Wnt Signalling and Epithelial-Mesenchymal Transition in Human OSCC

Shan Wang1, Haixia Fan2, Jie Bai3

  • 1Department of Oral Pathology, School of Stomatology, Hainan Medical University, Haikou, P. R. China.

Insights

Human interferon-inducible protein X (IFIX) inhibits oral cancer progression by suppressing epithelial-mesenchymal transition (EMT) via the NKD2-Wnt signaling pathway. This discovery offers new therapeutic targets for oral squamous cell carcinoma (OSCC).

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • The human interferon-inducible protein X (IFIX) isoform plays a role in cytoskeleton stability and inhibiting epithelial-mesenchymal transition (EMT).
  • The precise mechanisms of IFIX in oncogenesis, particularly in oral squamous cell carcinoma (OSCC), remain unclear.

Purpose of the Study:

  • To investigate the effects of IFIX overexpression and knockdown on OSCC cells.
  • To elucidate the molecular pathways, including Wnt signaling and NKD2, involved in IFIX-mediated oncogenesis.

Main Methods:

  • Utilized CAL-27 and SCC-25 OSCC cell lines for IFIX overexpression and knockdown experiments.
  • Employed quantitative reverse-transcription PCR and Western blotting to analyze gene and protein expression.
  • Investigated the roles of E-cadherin, N-cadherin, vimentin, Snail, Wnt signaling components, and NKD2.

Main Results:

  • IFIX modulation significantly altered the expression of EMT markers (E-cadherin, N-cadherin, vimentin, Snail) and Wnt signaling components.
  • A strong positive correlation was observed between IFIX and NKD2 expression, with both showing modulated expression upon IFIX manipulation.
  • NKD2 silencing mimicked IFIX knockdown effects and reversed IFIX overexpression's anticarcinogenic phenotype, impacting cell proliferation, invasion, and migration.

Conclusions:

  • IFIX exerts antioncogenic effects in OSCC by inhibiting EMT through the NKD2-mediated suppression of Wnt signaling.
  • These findings reveal a novel mechanism for IFIX's role in restricting cancer progression and highlight NKD2 as a key mediator.

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