FOXC2/ADAM12-dependent radiosensitivity of head and neck squamous cell carcinoma cells

Head Neck. 2022 Jan;44(1):212-225. doi: 10.1002/hed.26918. Epub 2021 Nov 3.

Abstract

Background: Radiotherapy greatly benefits patients with tumors, but not all patients show favorable treatment response. This study investigated the impact of forkhead box protein C2 (FOXC2)-mediated a disintegrin and metalloprotease 12 (ADAM12) on the radiosensitivity of head and neck squamous cell carcinoma (HNSCC).

Methods: After transfection and ionizing radiation, the biological activities of HNSCC cells were assessed. The relationship between ADAM12 and FOXC2 was verified. A xenograft model was used to evaluate the effect of FOXC2 knockdown on HNSCC growth in the context of radiation therapy.

Results: FOXC2 and ADAM12 were upregulated in irradiated CAL-27 and HN4 cells. Knockdown of FOXC2 suppressed the malignant behaviors of CAL-27 and HN4 cells and inhibited the growth of transplanted tumors in nude mice. FOXC2 could bind ADAM12 promoter. Overexpression of ADAM12 reversed the promotion of FOXC2 silencing on the radiosensitivity of HNSCC cells.

Conclusions: FOXC2 regulates the radiosensitivity of HNSCC by targeting ADAM12.

Keywords: disintegrin and metalloprotease 12; forkhead box protein C2; head and neck squamous cell carcinoma; invasion; migration; proliferation; radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM12 Protein
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Mice
  • Mice, Nude
  • Radiation Tolerance / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy

Substances

  • ADAM12 Protein
  • ADAM12 protein, human