title: The protein ERp57 contributes to EGF receptor signaling and internalization in MDA-MB-468 breast cancer cells.
abstract: The disulfide isomerase ERp57 is a soluble protein mainly located in the endoplasmic reticulum, where it acts in the quality control of newly synthesized glycoproteins, in association with calreticulin and calnexin. It has been also detected in other cell compartments, such as the cytosol, the plasma membrane and the nucleus. In these locations it is implicated in various processes, participating in the rapid response to calcitriol, modulating the activity of STAT3 and being requested for the pre-apoptotic exposure of calreticulin on the plasma membrane. In the present work, the involvement of ERp57 in the activity of the EGF receptor was evaluated for the first time. EGFR is a tyrosine kinase receptor, which is able to activate numerous signaling cascades, leading to cell proliferation and inhibition of apoptosis. In the MDA-MB-468 breast adenocarcinoma cells, which overexpress EGFR, ERp57 expression has been knocked down by siRNA and the effects on EGFR have been studied. ERp57 silencing did not affect EGFR protein expression, cell membrane exposure or EGF binding, whereas the internalization and the phosphorylation of the receptor were impaired. The implication of ERp57 in the activity of EGFR, whose upregulation is known to be associated with tumors, could be relevant for cancer therapy.
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gaucci
authors.forename: Fabio
authors.initials: F
authors.lastname: Altieri
authors.forename: Carlo
authors.initials: C
authors.lastname: Turano
authors.forename: Silvia
authors.initials: S
authors.lastname: Chichiarelli
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D066246:ErbB Receptors; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
keywords: EGFR ACTIVATION; IMMUNOFLUORESCENCE; RECEPTOR ENDOCYTOSIS; RNA INTERFERENCE; SIGNAL TRANSDUCTION