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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

10.9K

Chromatin regulation at the intersection of estrogen receptor and PI3K pathways in breast cancer

Pau Castel1,2, Eneda Toska1

  • 1Human Oncology & Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Molecular & Cellular Oncology
|November 7, 2019
PubMed

Insights

Breast cancer involves crosstalk between Estrogen Receptor (ER) and PI3K pathways. Chromatin regulation links these pathways, with AKT/PKB and SGK phosphorylating KMT2D to affect ER activity and treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Estrogen Receptor (ER) and phosphoinositide 3-kinase (PI3K) signaling pathways are critical in breast cancer development.
  • Crosstalk between ER and PI3K pathways influences tumor progression and therapeutic response.

Purpose of the Study:

  • To investigate the role of chromatin regulation at the intersection of ER and PI3K signaling in breast cancer.
  • To identify key molecular players mediating the interaction between these pathways.

Main Methods:

  • Utilized molecular biology techniques to study protein interactions and signaling pathways.
  • Investigated the phosphorylation of chromatin regulators by PI3K effectors.
  • Assessed the impact on Estrogen Receptor activity and therapy resistance.

Main Results:

  • Chromatin regulation was identified as a central point connecting oncogenic PI3K and ER signaling.
  • The PI3K effectors AKT (protein kinase B) and SGK were found to play redundant roles.
  • AKT/PKB and SGK phosphorylate the chromatin regulator KMT2D, modulating ER activity and contributing to therapy resistance.

Conclusions:

  • Chromatin regulation is a key mediator of ER and PI3K pathway crosstalk in breast cancer.
  • The AKT/PKB and SGK-KMT2D axis represents a potential therapeutic target for overcoming resistance.
  • Understanding this interaction is crucial for developing novel breast cancer treatment strategies.
Keywords:
AKT1KMT2DPI3K inhibitorsPI3K pathwaySGK1breast cancerchromatin regulationestrogen receptortherapy resistance

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