Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

Abstract

AbstractUbiquilin proteins (UBQLNs) are involved in diverse cellular processes like ERAD (endoplasmic reticulum associated degradation), autophagy, apoptosis and epithelial to mesenchymal transition. UBQLNs interact with a variety of substrates, including cell surface receptors, transcription factor regulators, proteasomal machinery proteins, and transmembrane proteins. Additionally, previous work from our lab shows that UBQLN1 interacts with IGFR family members (IGF1R, IGF2R, INSR) and this interaction regulates the activity and proteostasis of IGFR family members. Here, we examined regulation of UBQLN1 with Epidermal Growth Factor Receptor (EGFR) in lung adenocarcinoma cells. Loss of UBQLN1 occurs at high frequency in human lung cancer patient samples and we have shown that loss of UBQLN1 is capable altering processes involved in cell proliferation, migration, invasion and epithelial to mesenchymal transition in lung adenocarcinoma cell lines. Here, we present data that loss of UBQLN1 resulted in increased turnover of total EGFR, whilst increasing the relative amount of active EGFR in lung adenocarcinoma cells, especially in the presence of its ligand EGF. Furthermore, loss of UBQLN1 led to a more invasive cell phenotype as manifested by increased proliferation, migration and speed of movement of these lung adenocarcinoma cells. Taken together, UBQLN1 regulates expression and stability of IGFRs and EGFR, members of the receptor tyrosine kinase family of proteins in lung cancer cells.