Transcriptional activation of PPP1R14C by KLF7 unleashes CDK1 activity to promote lung squamous cell carcinoma

Lihua Xing1, Chunluan Yuan2, Xiaozhu Shen3

  • 1Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi Province, China.

Scientific Reports
|February 16, 2026
PubMed

Insights

Protein Phosphatase 1 Regulatory Subunit 14C (PPP1R14C) drives lung squamous cell carcinoma (LUSC) by inhibiting PP1, leading to CDK1 hyperactivation. Targeting this pathway offers a new therapeutic strategy for LUSC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Lung squamous cell carcinoma (LUSC) lacks targeted therapies, necessitating identification of new molecular drivers.
  • Protein Phosphatase 1 Regulatory Subunit 14C (PPP1R14C) is an endogenous inhibitor of Protein Phosphatase 1 (PP1).

Purpose of the Study:

  • To identify novel oncogenic drivers in LUSC.
  • To elucidate the role of PPP1R14C in LUSC pathogenesis.
  • To explore the KLF7-PPP1R14C-PP1-CDK1 signaling pathway as a therapeutic target.

Main Methods:

  • Integrative multi-omics analyses to assess PPP1R14C expression in LUSC.
  • ChIP assays to determine KLF7 binding to the PPP1R14C promoter.
  • Co-immunoprecipitation to study PPP1R14C-PP1 interaction.
  • In vitro and in vivo assays to evaluate the functional role of PPP1R14C and CDK1 inhibition.

Main Results:

  • PPP1R14C is significantly overexpressed in LUSC, correlating with advanced stage and poor survival.
  • KLF7 directly drives PPP1R14C expression.
  • PPP1R14C inhibits PP1, leading to sustained CDK1 hyperactivation, promoting LUSC cell proliferation, invasion, and tumorigenesis.
  • Pharmacological inhibition of CDK1 reverses PPP1R14C-mediated oncogenic phenotypes.

Conclusions:

  • A novel KLF7-PPP1R14C-PP1-CDK1 signaling axis is critical for LUSC pathogenesis.
  • PPP1R14C acts as a pivotal oncogenic driver in LUSC.
  • PPP1R14C is a potential prognostic biomarker and a promising therapeutic target for LUSC.

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