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.

MicroRNA-148a inhibits the proliferation and promotes the paclitaxel-induced apoptosis of ovarian cancer cells by targeting PDIA3

“…Downregulation of the expression of PDIA3 is associated with a poor prognosis in early-stage cervical cancer (21). In addition, PDIA3 was found to contribute to epidermal growth factor receptor signaling and internalization in breast cancer cells (22). A previous study demonstrated that PDIA3 is involved in paclitaxel resistance in ovarian cancer by interacting with class III β-tubulin (23).…”

Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

“…PDIA3 is involved in cell proliferation and stabilizing receptors on the cell membrane (19,20) and intracellular signaling molecules, including signal transducer and activator of transcription 3 (21) and mechanistic target of rapamycin (22). In hepatocellular carcinoma, high expression of PDIA3 was associated with high proliferative activity and low apoptotic cell death, whereas low expression was associated low proliferative activity and high apoptotic cell death (8,9).…”

PDIA3 and PDIA6 gene expression as an aggressiveness marker in primary ductal breast cancer

“…It has also been linked to DNA repair as a member of the damage recognition complex and as a potential regulator that binds to genes with recognized repair functions (Chichiarelli et al, 2007). Several studies have linked PDIs to different types of cancer, including gastric (Leys et al, 2007), prostate (Pressinotti et al, 2009), esophageal (Ayshamgul et al, 2011), cervical (De Marco et al, 2012;Chung et al, 2013), salivary gland (Müller et al, 2013), bone metastasis (Santana-Codina et al, 2013), and breast (Lee et al, 2012;Gaucci et al, 2013) cancers. Another gene in this superfamily, PDIA6, also encodes a product that exhibits chaperone activity by inhibiting misformed protein aggregation.…”