G protein-coupled oestrogen receptor regulates branched-chain amino acid metabolism through c-Jun N-terminal kinase.

Branched-chain amino acids (BCAA) are essential requirements for overall protein turnover, signalling and energy balance, and dysregulation of their metabolic pathway has been associated with many pathophysiological events. Despite the importance of BCAA in human health, our understanding of their metabolic regulation is limited. Here, we present evidence that G protein-coupled oestrogen receptor (GPER) activation inhibits the key BCAA metabolic regulatory enzyme branched-chain α-keto acid dehydrogenase complex (BCKDH) by phosphorylating S293.

Tamoxifen modulates nutrition deprivation-induced ER stress through AMPK-mediated ER-phagy in breast cancer cells.

Purpose: Rapid proliferation and nutrition starvation in the tumor microenvironment pose significant challenges to cellular protein homeostasis. The accumulation of misfolded proteins in the endoplasmic reticulum lumen induces stress on cells and causes irreversible damage to cells if unresolved. Emerging reports emphasize the influence of the tumor microenvironment on therapeutic molecule efficacy and treatment outcomes.