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Identification and validation of dysregulated MAPK7 (ERK5) as a novel oncogenic target in squamous cell lung and

Paul R Gavine1, Mei Wang2, Dehua Yu3

  • 1Innovation Center China, AstraZeneca Global R&D, Zhangjiang Hi-Tech Park, Shanghai, 201203, People's Republic of China. Paul.gavine@astrazeneca.com.

BMC Cancer
|June 5, 2015
PubMed
Abstract

Insights

MAPK7 (mitogen activated protein kinase 7) gene amplification drives cancer in specific patient groups. Researchers identified new biomarkers and screening methods for MAPK7-targeted therapies.

Area of Science:

  • Molecular Biology
  • Oncology

Background:

  • MAPK7 (mitogen activated protein kinase 7), also known as ERK5 (extracellular-signal-regulated kinase 5), is part of a key signaling pathway implicated in cancer.
  • While less studied than other MAPK pathways, MAPK7 signaling is increasingly recognized for its role in various cancer pathologies.

Purpose of the Study:

  • To investigate the role of MAPK7 gene amplification and protein expression in non-small cell lung cancer (NSCLC) and squamous esophageal cancer (sqEC).
  • To validate MAPK7 as a potential oncogenic driver and develop screening methods for targeted therapies.

Main Methods:

  • Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were used to detect MAPK7 gene amplification and protein levels.
  • In vitro siRNA knockdown experiments validated MAPK7's role in tumor cell proliferation.
  • A novel cell line was developed for pharmacodynamic screening, and phosphorylation antibody microarrays identified downstream biomarkers.

Main Results:

  • MAPK7 gene amplification was found in 4% of NSCLC (6% in squamous cell carcinoma) and 2% of squamous esophageal cancers.
  • A strong correlation was observed between MAPK7 gene amplification and protein expression.
  • siRNA knockdown confirmed MAPK7 as a proliferative oncogenic driver. Novel downstream biomarkers (pMEF2A, pMEF2D) for MAPK7 inhibition were identified.

Conclusions:

  • Dysregulated MAPK7 plays a significant role in tumorigenesis in specific cancer populations.
  • The study established a screening cascade for drug discovery targeting MAPK7, highlighting its potential as a therapeutic target.

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