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KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells

Ying Du1, Hui Ye1, Mei Lin2

  • 1Oncology Department, Shandong Provincial Qianfoshan Hospital, School of Medicine, Shandong University, Jinan, China.

Frontiers in Immunology
|December 25, 2023
PubMed
Abstract

Insights

Krüppel-like factor 14 (KLF14) induces S-phase arrest in cervical cancer cells, inhibiting proliferation. This effect is mediated by the JNK signaling pathway, impacting cell cycle regulators like CDK2 and CCNA2.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell cycle regulation

Background:

  • Cervical cancer remains a significant global health concern.
  • Understanding the molecular mechanisms governing cervical cancer cell proliferation is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of Krüppel-like factor 14 (KLF14) in cervical cancer cell cycle regulation.
  • To elucidate the underlying molecular mechanisms, including the involvement of the JNK signaling pathway.

Main Methods:

  • Lentiviral vectors were used to overexpress KLF14 and its mutants in SiHa and HeLa cervical cancer cells.
  • Cell cycle progression was analyzed using flow cytometry.
  • Gene and protein expression of cell cycle regulators (CDK2, CCNA2) and MAPK pathway components (p-JNK/JNK) were assessed via qRT-PCR and Western blotting.
  • In vivo studies using subcutaneous xenografts evaluated the effect of KLF14 on tumor proliferation.

Main Results:

  • KLF14 overexpression led to increased S-phase arrest and elevated expression of CDK2, CCNA2, and p-JNK/JNK.
  • Inhibition or promotion of the JNK pathway modulated S-phase arrest and the expression of CDK2 and CCNA2.
  • In vivo, KLF14 inhibited cervical cancer cell proliferation and increased the expression of p-JNK/JNK, CDK2, and CCNA2 in tumors.

Conclusions:

  • KLF14 induces S-phase arrest in cervical cancer cells, dependent on its zinc-finger structure.
  • KLF14 activates the JNK signaling pathway, promoting S-phase arrest and upregulating CDK2 and CCNA2 expression.
  • KLF14 inhibits cervical cancer cell proliferation in vivo, highlighting its potential as a therapeutic target.
Keywords:
CDK2KLF14MAPK-signaling pathwaycell cyclecervical cancer

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