High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma

Abstract

Valosin-containing protein (VCP) is one of the AAA-ATPase superfamily members. The correlation between elevated expression of VCP and progression, prognosis, and the metastatic potential has been identified in various tumor types. However, the clinical impact of VCP in breast carcinoma has not been investigated. In the current study, the expression of VCP in 421 breast tumors and adjacent normal breast tissues was examined to investigate the correlation between VCP expression and clinicopathological features in patients with breast carcinoma. We found that the expression of VCP correlated with the TNM stage, Ki67 labeling, and lymph node metastasis (LNM). The expression of VCP was increased significantly in the cytoplasm of cancer cells compared to normal mammary epithelial cells, which was associated with decreased overall survival rates of patients with breast carcinoma (P < 0.001). In conclusion, this study demonstrates significant correlation between the cytoplasmic expression of VCP and adverse prognosis in breast carcinoma, suggesting that VCP may serve as a prognostic biomarker in breast carcinoma.

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

“…Our results support the notion that the p97/NPL4 pathway is a promising therapeutic target in oncology 45 , 46 . Indeed, reports on p97 overabundance correlating with progression and metastasis of carcinomas of the breast, colon, and prostate 47 – 49 are consistent with our present nationwide epidemiological analysis revealing an association between continued use of DSF and favourable prognosis, an intriguing finding worthy of further investigation, particularly given the currently limited therapeutic options for patients with metastatic cancer. From a broader perspective, our study illustrates the potential of multifaceted approaches to drug repositioning, providing novel mechanistic insights, identification of new cancer-relevant targets and inspiration for clinical trials, here with DSF, an old, safe and public domain drug 4 that might help save lives of cancer patients worldwide.…”

Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer

“…The pleiotropic functions and involvement in the maintenance of protein homeostasis attracted much attention to the VCP as a putative anticancer therapy target (266, 267). Indeed, the VCP is upregulated in many different tumors (colorectal, gastric, hepatocellular, breast, non-smal-cell lung, and esophagal squamous cell carcinomas, pancreatic endocrine cancer, prostate and follicular thyroid cancers) and its expression is associated with the poor prognosis (268, 269). Interestingly, the molecular mechanisms by which VCP promotes cancer growth, progression and invasion are at least in part associated with stimulation of UPS-mediated degradation of important regulatory proteins including IκB (NFκB inhibitor) (270–272) and p53 (272, 273).…”

A robust strategy for proteomic identification of biomarkers of invasive phenotype complexed with extracellular heat shock proteins

“…Other chaperones were prominent in extracellular HSP complexes ( Table 2). All three sources contained abundant endoplasmic reticulum ATPase p97 (VCP) central to invasive phenotype (Cui et al 2015;Fu et al 2016) and modulation of proteotoxicity (Vekaria et al 2016;Gugliotta et al 2017). Protein disulfide isomerases P4HB and PDIA3 as well as peptidyl prolyl isomerases were also significant as exported chaperome components (Perrucci et al 2015;Lee and Lee 2017;Zou et al 2017;Stifani 2018).…”