Frontiers in oncology
Secretory carrier membrane protein 3 modulates nuclear ERK1/2 signaling and drug response in triple-negative breast cancer
By Morales-Cabán BM, Jackson-González M, Acosta-Pérez FA and 2 others.
Abstract
Introduction
Triple-negative breast cancer (TNBC) frequently displays hyperactive mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases 1/2 (ERK1/2) signaling but lacks tractable targets to sustain durable pathway inhibition. Identifying modulators that shape ERK1/2 output and influence responses to ERK1/2 inhibitors is therefore needed. The endosomal trafficking protein secretory carrier membrane protein 3 (SCAMP3) is a positive regulator of epidermal growth factor receptor (EGFR) signaling and ERK1/2-dependent phosphoproteomics programs in TNBC. However, the mechanism by which SCAMP3 modulates ERK1/2 signaling and targeted drug response remains unclear.
Methods
Here, we combined SCAMP3 knockout with pharmacological ERK1/2 inhibition to evaluate SCAMP3's contributions to MAPK signaling, ERK1/2 distribution, cell-cycle control, apoptosis, and in vivo drug response.