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Inhibitor of DNA Binding 2 (ID2): A Novel Marker for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma

  • Translational Research
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although aggressive invasion and sequential lymph node metastasis (LNM) significantly affect the prognosis of patients with head and neck squamous cell carcinoma (HNSCC), studies on identifying the factors that regulate this process remain scarce. This study found an inhibitor of DNA binding 2 (ID2) as a novel molecule involved in the regulation of invasion and LNM of HNSCC and further verified its functional role.

Methods

The study examined the translational significance between ID2 expression levels and the presence of LNM as well as the prognosis for 119 patients with HNSCC after treatment. In addition, in vitro and in vivo experiments were performed using ID2 gene-modulated HNSCC cell lines to determine the functional role of ID2 in the invasion and LNM of HNSCC.

Results

Elevated levels of ID2 expression were closely associated with the presence of LNM in 119 patients with HNSCC, resulting in a poor prognosis. Overexpression of ID2-induced invasion and LNM of HNSCC cells was observed in vitro and in vivo. By contrast, knockdown of the ID2 gene diminished invasion and LNM of HNSCC cells. In addition, the ID2 expression level increased the expression level of matrix metalloproteinase 1 (MMP1), a molecule downstream to ID2. Furthermore, silencing of MMP1 in ID2-overexpressed HNSCC cells rescued the elevated invasion and LNM capabilities of these cells, suggesting that ID2 enhances invasion and LNM partly via MMP1 activation.

Conclusion

In the invasion and LNM of HNSCC, ID2 plays an important role by modulating MMP1 expression, suggesting ID2-MMP1 axis to be a novel alternative therapeutic target for invasion and LNM of HNSCC.

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Acknowledgment

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MEST) (NRF-2016R1A5A2012284), by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1A02086084), and by the Technology Innovation Program funded by the Ministry of Trade, Industry & Energry (20009773).

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  1. Hye Ryun Kim and Jung Hwa Moon have contributed equally to this paper.

Authors and Affiliations

  1. Department of Otorhinolaryngology – Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea

    Hye Ryun Kim MS, Jung Hwa Moon PhD, Jun Hwan Lee PhD & Young Chang Lim MD, PhD

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  1. Hye Ryun Kim MS
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  2. Jung Hwa Moon PhD
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Correspondence to Young Chang Lim MD, PhD.

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Kim, H.R., Moon, J.H., Lee, J.H. et al. Inhibitor of DNA Binding 2 (ID2): A Novel Marker for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma. Ann Surg Oncol 28, 6479–6488 (2021). https://doi.org/10.1245/s10434-021-09832-z

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  • DOI: https://doi.org/10.1245/s10434-021-09832-z

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