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Updated: Sep 30, 2025
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Snail Augments Nuclear Deformability to Promote Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma
Yin-Quan Chen1, Chen-Yu Hung2, Ming-Tzo Wei3
1Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Abstract:
Up to 50% of head and neck squamous cell carcinoma (HNSCC) patients have lymph node (LN) metastasis, resulting in poor survival rate. Numerous studies have supported the notion that the alterations of gene expression and mechanical properties of cancer cells play an important role in cancer metastasis. However, which genes and how they regulate the biomechanical properties of HNSCC cells to promote LN metastasis remains elusive. In this study, we used an LN-metastatic mouse model in vivo to generate an LN-metastatic head and neck squamous cell carcinoma cell line and compared the differences in the biomolecular and biomechanical properties of LN-metastatic and non-metastatic cells. Our results showed that LN-metastatic cells had a higher level of Snail expression compared to non-LN-metastatic cells. The higher Snail expression promoted the cellular invasion capability in confined environments, mainly by increasing the longitudinal strain of the cell nuclei, which could be attributed to the stronger cell traction force and softer nuclear stiffness. These two biomechanical changes were correlated, respectively, to a larger amount of focal adhesion and less amount of nuclear lamins. Taken together, our works revealed not only the biomechanical profiles of LN-metastatic cells but also the corresponding biomolecular expressions to pinpoint the key process in LN metastasis.
Insights
Head and neck squamous cell carcinoma (HNSCC) cells with higher Snail expression show increased invasion. This is due to altered nuclear mechanics, promoting lymph node metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Cellular Biomechanics
Background:
- Lymph node metastasis significantly worsens survival in head and neck squamous cell carcinoma (HNSCC).
- Gene expression and cellular mechanical properties are implicated in cancer metastasis, but specific mechanisms in HNSCC remain unclear.
Purpose of the Study:
- To investigate the biomolecular and biomechanical differences between lymph node-metastatic and non-metastatic HNSCC cells.
- To identify key genes and cellular mechanisms driving HNSCC lymph node metastasis.
Main Methods:
- Generation of an LN-metastatic HNSCC cell line using an *in vivo* mouse model.
- Comparative analysis of biomolecular and biomechanical properties between metastatic and non-metastatic HNSCC cells.
Main Results:
- LN-metastatic HNSCC cells exhibit significantly higher Snail expression compared to non-metastatic cells.
- Elevated Snail expression enhances cellular invasion in confined spaces by increasing nuclear longitudinal strain.
- This nuclear strain is linked to increased cell traction force, softer nuclear stiffness, more focal adhesions, and fewer nuclear lamins.
Conclusions:
- Snail expression is a key regulator of HNSCC cell biomechanics and invasion.
- Altered nuclear properties, driven by Snail, are crucial for promoting lymph node metastasis in HNSCC.
- This study elucidates the biomechanical profile and molecular drivers of metastatic HNSCC cells.
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