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.

Molecular Carcinogenesis
|November 6, 2024
PubMed

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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