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Updated: Jun 8, 2025

Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
NEK2 Promotes ESCC Malignant Progression by Inhibiting Cellular Senescence via the FOXM1/c-Myc/p27 Signaling Pathway
Jiachen Li1, Yaojie Wang2,3, Sisi Wei2,3
1Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Abstract:
Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a crucial serine-threonine kinase involved in the process of cell mitosis. However, the precise relationship between NEK2 and esophageal squamous cell carcinoma (ESCC) remains inadequately understood. NEK2 expression in ESCC tissues was assessed through bioinformatics analysis, reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry, revealing a correlation with ESCC patient prognosis. Cultured ESCC cells and human normal esophageal epithelial cells (HEEC) were used to investigate the effects of NEK2 knockdown on the development and progression of ESCC by integrated confluence algorithm, colony formation, wound-healing, transwell, and ESCC xenograft tumor model, in vitro and in vivo. In ESCC tissues, NEK2 was found to be significantly upregulated, and its expression correlated with poor prognosis in ESCC patients. NEK2 may facilitate ESCC development by regulating cell proliferation, migration, and invasion. Additionally, results from in vivo experiments suggested that NEK2 knockdown can inhibit tumor growth. Moreover, forkhead box M1 (FOXM1) was identified as a potential downstream target of NEK2 in the regulation of ESCC, with its overexpression reversing the effects of NEK2 knockdown on ESCC. Mechanistic studies also indicated that NEK2 may promote the malignant progression of ESCC by inhibiting cellular senescence through the activation of the FOXM1/c-Myc/p27 signaling pathways, which may provide a novel perspective for the management of ESCC.
Insights
Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is upregulated in esophageal squamous cell carcinoma (ESCC). NEK2 inhibition suppresses ESCC progression by affecting proliferation, migration, and invasion via the FOXM1/c-Myc/p27 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a serine-threonine kinase vital for cell mitosis.
- The specific role of NEK2 in esophageal squamous cell carcinoma (ESCC) pathogenesis is not fully elucidated.
- Understanding NEK2's function in ESCC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression and function of NEK2 in ESCC.
- To determine the relationship between NEK2 expression and patient prognosis.
- To elucidate the molecular mechanisms by which NEK2 influences ESCC progression.
Main Methods:
- Bioinformatics analysis, RT-qPCR, and immunohistochemistry were used to assess NEK2 expression in ESCC tissues.
- In vitro assays (cell proliferation, colony formation, migration, invasion) and in vivo xenograft models were employed to study NEK2 knockdown effects.
- Western blotting and signaling pathway analysis identified downstream targets and mechanisms.
Main Results:
- NEK2 expression is significantly upregulated in ESCC tissues and correlates with poor patient prognosis.
- NEK2 knockdown inhibited ESCC cell proliferation, migration, and invasion in vitro and reduced tumor growth in vivo.
- NEK2 promotes ESCC progression by activating the FOXM1/c-Myc/p27 signaling pathway, inhibiting cellular senescence.
Conclusions:
- NEK2 is a key driver of ESCC progression, acting through the FOXM1/c-Myc/p27 pathway.
- Targeting NEK2 may offer a novel therapeutic strategy for managing esophageal squamous cell carcinoma.
- NEK2 inhibition presents a promising avenue for improving outcomes in ESCC patients.
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