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Updated: Jun 1, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
The activation of the human interferon-inducible protein X (IFIX) isoform is associated with maintaining a stable cytoskeleton and inhibiting epithelial-mesenchymal transition (EMT). However, the mechanisms and pathways underlying IFIX-mediated oncogenesis are not well understood. In this study, we investigated the effects of IFIX overexpression and knockdown in CAL-27 and SCC-25 oral squamous cell carcinoma (OSCC) cells. We observed significant variations in the expression of E-cadherin, N-cadherin, vimentin and Snail, as well as changes in wingless/integrated (Wnt) signalling. Our results indicated a strong correlation between IFIX and EMT, as evidenced by quantitative reverse-transcription PCR and Western blotting, which revealed that Wnt3a and Wnt4 pathway components were regulated in IFIX-overexpressing or knockdown cells, with naked cuticle 2 (NKD2) showing the strongest positive correlation. Both IFIX overexpression and knockdown modulated NKD2 expression. NKD2 silencing mimicked the phenotypic effects of IFIX knockdown, inhibiting E-cadherin expression and increasing N-cadherin, Snail and vimentin expression. Additionally, silencing NKD2 restored the anticarcinogenic phenotype associated with IFIX overexpression, affecting cell proliferation, invasion and migration. These findings provide mechanistic insights into the antioncogenic effects of IFIX in OSCC, involving the inhibition of Wnt signalling through NKD2, which leads to cancer-inhibiting phenotypic effects, including restricted EMT.
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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