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Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment
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MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors

Sofia S Pereira1,2,3, Mariana P Monteiro3, Madalena M Costa3

  • 1Cancer Signalling & Metabolism, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Portugal.

Journal of Cellular Biochemistry
|September 27, 2018
PubMed

Insights

Mitogen-activated protein kinase (MAPK) signaling, specifically extracellular signal-regulated protein kinases (ERKs 1/2), is elevated in malignant adrenocortical tumors. Inhibiting this pathway may offer a targeted treatment for adrenocortical carcinoma (ACC).

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Adrenocortical carcinomas (ACC) have high mortality rates, necessitating research into their molecular mechanisms.
  • Mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated protein kinases (ERKs 1/2) and p38, are implicated in cellular processes relevant to tumorigenesis.

Purpose of the Study:

  • To investigate the role of ERK1/2 and p38 MAPK pathways in adrenocortical tumorigenesis.
  • To evaluate the therapeutic potential of inhibiting the MAPK/ERK pathway in ACC.

Main Methods:

  • Assessed ERK1/2 and p38 activation in normal adrenal glands (NAG), incidentalomas (INC), benign Cushing's syndrome (BCS), and malignant Cushing's syndrome (MCS).
  • Utilized the ACC cell line (H295R) to test the effects of PD184352, a MEK-MAPK-ERK inhibitor, on proliferation, viability, metabolism, and steroidogenesis.

Main Results:

  • ERK1/2 activation was significantly higher in MCS compared to NAG, INC, and BCS.
  • Phospho-p38 expression was not detected in any of the analyzed MCS samples.
  • MEK inhibition with PD184352 reduced H295R cell proliferation and steroidogenesis, while increasing cellular redox state.

Conclusions:

  • The MEK-MAPK-ERK signaling pathway plays a role in adrenocortical tumorigenesis.
  • Elevated ERK1/2 activation may serve as a diagnostic marker for ACC malignancy.
  • Targeting the MEK-MAPK-ERK pathway presents a potential therapeutic strategy for ACC.
Keywords:
adrenocortical carcinoma (ACC)adrenocortical tumorscancer treatmentmitogen-activated protein kinase/extracellular signal-regulated protein kinases (MAPK/ERK) pathway

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