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Updated: Feb 10, 2026

Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry
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Measurement of Protein Turnover Rates in Senescent and Non-Dividing Cultured Cells with Metabolic Labeling and Mass Spectrometry

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PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence

Mary E Klein1,2, Mark A Dickson3,4, Cristina Antonescu5

  • 1The Louis V. Gerstner Graduate School of Biomedical Science, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Oncogene
|May 24, 2018
PubMed

Insights

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors induce tumor cell senescence by downregulating MDM2 protein. CDH18 protein expression correlates with patient response to CDK4/6 inhibitors, indicating clinical relevance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are emerging therapies for human malignancies.
  • These inhibitors show promise in liposarcoma by downregulating MDM2 protein.
  • CDK4/6 inhibition can induce tumor cell lines to enter senescence from quiescence.

Purpose of the Study:

  • To define the role of PDLIM7 and CDH18 in regulating MDM2 protein in CDK4/6 inhibitor-treated cells.
  • To investigate the clinical relevance of the quiescence-to-senescence transition in response to CDK4/6 inhibitors.

Main Methods:

  • Utilized cultured human cell lines to identify key regulatory proteins.
  • Analyzed patient data from phase II trials of palbociclib.
  • Correlated CDH18 protein expression with progression-free and overall survival.

Main Results:

  • Identified PDLIM7 and CDH18 as regulators of MDM2 protein in CDK4/6 inhibitor-treated cells.
  • Demonstrated that CDH18 protein expression is associated with improved progression-free survival and overall survival in patients treated with palbociclib.
  • Established a link between the cellular response (senescence) and clinical outcomes.

Conclusions:

  • PDLIM7 and CDH18 play a role in MDM2 regulation during CDK4/6 inhibition.
  • CDH18 expression serves as a predictive biomarker for response to CDK4/6 inhibitors.
  • The induction of senescence is a clinically relevant mechanism for CDK4/6 inhibitor efficacy.

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