Quantitative proteomics analysis identifies MUC1 as an effect sensor of EGFR inhibition

H Rudolf de Boer, Martin Pool, Esméé Joosten, Marieke Everts, Douwe F Samplonius, Wijnand Helfrich, Harry J M Groen, Suzanne van Cooten, Fabrizia Fusetti, Rudolf S N Fehrmann, Elisabeth G E de Vries, Marcel A T M van Vugt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Tumor responses to cancer therapeutics are generally monitored every 2-3 months based on changes in tumor size. Dynamic biomarkers that reflect effective engagement of targeted therapeutics to the targeted pathway, so-called "effect sensors", would fulfill a need for non-invasive, drug-specific indicators of early treatment effect. Using a proteomics approach to identify effect sensors, we demonstrated MUC1 upregulation in response to epidermal growth factor receptor (EGFR)targeting treatments in breast and lung cancer models. To achieve this, using semi-quantitative mass spectrometry, we found MUC1 to be significantly and durably upregulated in response to erlotinib, an EGFR-targeting treatment. MUC1 upregulation was regulated transcriptionally, involving PI3K-signaling and STAT3. We validated these results in erlotinib-sensitive human breast and non-small lung cancer cell lines. Importantly, erlotinib treatment of mice bearing SUM149 xenografts resulted in increased MUC1 shedding into plasma. Analysis of MUC1 using serial blood sampling may therefore be a new, relatively non-invasive tool to monitor early and drug-specific effects of EGFR-targeting therapeutics.

Original languageEnglish
Pages (from-to)1477-1488
Number of pages12
JournalONCOGENE
Volume38
Issue number9
Early online date10-Oct-2018
DOIs
Publication statusPublished - 28-Feb-2019

Keywords

  • LUNG-CANCER
  • UP-REGULATION
  • MET AMPLIFICATION
  • STAT3 ACTIVATION
  • DRUG DEVELOPMENT
  • EXPRESSION
  • RESISTANCE
  • FAMILY
  • GEFITINIB
  • PROGNOSIS

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