Proteome changes induced by overexpression of the p75 neurotrophin receptor (p75NTR) in breast cancer cells

Abstract

In breast cancer cells, the neurotrophin receptor p75NTR acts as a prosurvival factor able to stimulate resistance to apoptosis, but its mechanism of action remains incompletely defined. In this study, we investigated the global proteome modification induced by p75 NTR overexpression in breast cancer cells treated by the pro-apoptotic agent tumor necrosis factor (TNF)-related-apoptosis-inducing-ligand (TRAIL). p75 NTR was stably overexpressed in the MCF-7 breast cancer cells and the impact of a treatment by TRAIL was investigated in wild type vs. p75 NTR overexpressing cells. Proteins were separated in two-dimensional electrophoresis, and regulated spots were detected by computer assisted analysis before identification by MALDI-TOF/TOF mass spectrometry. In the absence of TRAIL treatment, p75 NTR did not induce any change in the proteome of breast cancer cells. In contrast, after treatment with TRAIL, fragments of cytokeratin-8, -18 and -19, as well as full length cytokeratin-18, were up-regulated by p75 NTR overexpression. Of note, spectrin alpha-chain and the ribosomal protein RPLP0 were induced by TRAIL, independently of p75 NTR level. Interestingly, the well known stress-induced protein HSP-27 was less abundant when p75 NTR was overexpressed, indicating that p75 NTR overexpression reduced TRAIL induced cell stress. These data indicate that overexpression of p75 NTR induces proteome modifications in breast cancer cells and provide information on how this receptor contributes in tumor cell resistance to apoptosis.

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

“…MalDi target plate (anchorchip™; Bruker Daltonics) was covered with extracted peptides mixed-up with α-cyano-4-hydroxycinnamic acid matrix (0.3 mg/ml in acetone:ethanol, 3:6 v/v). The molecular mass measurements were obtained as previously described (26). Database searches, through Mascot v.2.2.1 (Matrix Science, ltd., london, uK), using combined PMf and Pff datasets were performed against the unitProt 2013-06 database (2013-06-17) via ProteinScape 2.1 (Bruker Daltonics).…”

The low‐affinity nerve growth factor receptor p75NTR identifies a transient stem cell‐like state in oral squamous cell carcinoma cells

“…Although structurally belonging to the tumor necrosis factor receptor superfamily , many of the biological functions of p75NTR differ from other members of this family, and a role in promoting cell survival has been suggested in normal human oral mucosa (NHOM) and nerves . Furthermore, possible role of this molecule in carcinogenesis was suggested in laryngeal, prostate, and breast cancers . It has also been suggested as a marker of CSCs in malignant melanoma , esophageal carcinoma , and it was found to be a determinant of poor prognosis in OSCC .…”

CDPath: Cooperative Driver Pathways Discovery Using Integer Linear Programming and Markov Clustering

“…Driver Pathways of BRCA Driver Pathways of UCEC CDPath p57(NTR)-mediated signaling, [42] VEGFR3 signaling in lymphatic endothelium; [36] Class I PI3K signaling events mediated by Akt, [38] Class I PI3K signaling events, [40] Atypical NF-kappaB pathway; [37] Cabonical Wnt signaling pathway; [43] ErbB1 downstream signaling,ErbB2ErbB3 signaling events; [44] mTOR signaling pathway, [41] EGF receptor (ErbB1) signaling pathway, Notch signaling pathway; [36] Notch signaling pathway; IGF1 pathway, Integrins in angiogenesis; [45] Il2 signaling events mediated by PI3K, [40] p53 pathway, FoxO family signaling; [39] mTOR signaling pathway; [41] RAC1 signaling pathway, Class I PI3K signaling events; [38] Internalization of ErbB1, [44] p53 pathway, [46] Validated targets of C-MYC transcriptional activation; [47] IL2 signaling events mediated by STAT5;…”

“…Dendrix RAC1 signaling pathway, CDC42 signaling events, Class I PI3K signaling events, [40] Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) p53 pathway [46] BLP p53 pathway, [39] p75(NTR)-mediated signaling, [42] Glucocorticoid receptor regulatory network, p53 pathway [46] Validated targets of C-MYC transcriptional activation, [47] Integrins in angiogenesis Multi-Dendrix RAC1 signaling pathway, Class I PI3K signaling events, [40] Class I PI3K signaling events; [38] IL2 signaling events mediated by STAT5…”

“…CoMDP p53 pathway, ErbB1 downstream signaling; [39], [44] p53 pathway, p75(NTR)-mediated signaling; [42] Class I PI3K signaling events, [40] p53 pathway, Signaling events mediated IL2 signaling events mediated by PI3K; [40] by Hepatocyte Growth Factor Receptor (c-Met);…”