β2-AR activation promotes cleavage and nuclear translocation of Her2 and metastatic potential of cancer cells.

ABSTRACT: Prolonged hypersecretion of catecholamine induced by chronic stress may correlate with malignant progression of cancer. β2-adrenergic receptor (β2-AR) overexpressed in certain cancer cells may translate the signals from neuroendocrine system to malignant signals by interacting with oncoproteins, such as Her2. In the present study, we demonstrate that catecholamine stimulation activates the expression and proteolytic activity of ADAM10 by modulating the expression of miR-199a-5p and SIRT1 and also confirm that catecholamine induction triggers the activities of γ-secretase, leading to shedding of Her2 extracellular domain (ECD) by ADAM10 and subsequent intramembranous cleavage of Her2 intracellular domain (ICD) by presenilin-dependent γ-secretase, nuclear translocation of Her2 ICD, and enhan

SUBMITTER: Liu D 

PROVIDER: S-EPMC7734010 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature