ERK activation modulates invasiveness and Reactive Oxygen Species (ROS) production in triple negative breast cancer

Adilene Acosta-Casique1, José B Montes-Alvarado2, Minuet Barragán1

  • 1Centro de Investigación Biomédica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social (IMSS), Km 4.5 Carretera Atlixco-Metepec HGZ5, Puebla 74360, Mexico; Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla (BUAP), Ciudad Universitaria, Puebla 72570, Mexico.

Cellular Signalling
|October 10, 2022
PubMed

Insights

Triple negative breast cancer (TNBC) research reveals ERK pathway is crucial for cell migration and mitochondrial function. MEK inhibitor PD0325901 reduced reactive oxygen species and mitochondrial fragmentation in TNBC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple negative breast cancer (TNBC) presents a poor prognosis and lacks targeted therapies.
  • The mitogen-activated protein kinase (MAPK) signaling pathway, particularly ERK, is implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of the MEK/ERK pathway in TNBC.
  • To explore the effects of MEK inhibition on TNBC cell migration, mitochondrial dynamics, and reactive oxygen species (ROS) production.

Main Methods:

  • Analysis of ERK phosphorylation in TNBC cell lines.
  • Assessment of TNBC cell migration.
  • Evaluation of mitochondrial fragmentation and ROS levels following treatment with PD0325901 (a MEK inhibitor) and antioxidants.

Main Results:

  • Elevated ERK phosphorylation was observed in TNBC cell lines, correlating with sustained cell migration.
  • Antioxidant treatment paradoxically increased ERK phosphorylation, suggesting enhanced invasiveness.
  • PD0325901 treatment decreased ROS levels and mitochondrial fragmentation in MDAMB231 cells.

Conclusions:

  • The MEK/ERK pathway plays a significant role in TNBC.
  • Targeting MEK/ERK may offer a therapeutic strategy for TNBC by impacting cell migration, mitochondrial function, and ROS production.