Overexpression of PrPc, combined with MGr1‐Ag/37LRP, is predictive of poor prognosis in gastric cancer

Zhou, Lin; Shang, Yulong; Liu, Changhao; Li, Jinge; Hu, Hao; Liang, Cong; Han, Yanan; Zhang, Wei; Liang, Jie; Wu, Kaichun

doi:10.1002/ijc.28883

Cited by 38 publications

(45 citation statements)

References 38 publications

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“…miRNAs, including miR-27a, miR-497, miR-363, miR-181b, miR-15b and miR-16, have been reported to be implicated in the MDR of GC (Ishimoto et al, 2016;Riquelme et al, 2016;Song and Ajani, 2013;Xia et al, 2008;Zhang et al, 2016;Zhu et al, 2010). Our previous studies identified 11 miRNAs, which regulate MDR in GC, using high-throughput functional screening, and further confirmed that miR-27b/CCNG1/P53/miR-508-5p axis plays important roles in GC-associated MDR (Shang et al, 2016;Shang et al, 2014). Here we identified miR-20a as an upstream miRNA of LRIG1, playing an important role in GC 1 1 drug resistance.…”

Section: Discussionsupporting

confidence: 67%

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Zhou

Zhang

et al. 2017

Preprint

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Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells. Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues, was identified to regulate LRIG1 expression by directly targeting its 3'untranslated region. We also found that inhibition of miR-20a suppressed GC MDR, and up-regulation showed opposite effects. Moreover, we demonstrated that the miR-20a/LRIG1 axis regulated GC cell MDR through EGFR mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1 expression in human GC tissues is inversely correlated with miR-20a and EGFR. Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight into the MDR process of GC, and targeting this axis represents a novel potential therapeutic strategy to block GC chemo-resistance.

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Section: Discussionsupporting

confidence: 67%

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Zhou

Zhang

et al. 2017

Preprint

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“…Moreover, more recently it was suggested that PrP C might also promote human tumor development and diffusion, and the induction of drug resistance [22, 36]. PrP C overexpression was observed in gastric cancer lesions as compared to non-tumor tissues representing a predictive marker of poor prognosis [66], while PrP C down-regulation reduced tumor cell proliferation [67] or caused cell death via the activation of the autophagic pathway [68]. However, most of these studies have been performed in continuous cell lines evaluating the effects of PrP C on the biological behavior of the cells.…”

Section: Discussionmentioning

confidence: 99%

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

et al. 2016

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Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype.

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“…Indeed, Chieng and Say (2015) found that overexpression of PrP C in a colon adenocarcinoma cell line increased invasiveness, whilst a study of pancreatic ductal adenocarcinoma patients reported that PrP C -positive tumours were associated with reduced survival time from diagnosis (Sy et al, 2011). PrP C expression was also shown to be upregulated in cancerous tissue from human gastric cancer patients compared with adjacent non-cancerous tissue from the same individuals (Zhou et al, 2014), although a recent study of a larger patient group found the opposite correlation (Tang et al, 2016). …”

Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

169

157

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The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrPC into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrPC, allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrPC. In this review, we first summarise important aspects of the biochemistry of PrPC before moving on to address the current understanding of the various proposed functions of the protein, including details of the underlying molecular mechanisms potentially involved in these functions. Over years of study, PrPC has been associated with a wide array of different cellular processes and many interacting partners have been suggested. However, recent studies have cast doubt on the previously well-established links between PrPC and processes such as stress-protection, copper homeostasis and neuronal excitability. Instead, the functions best-supported by the current literature include regulation of myelin maintenance and of processes linked to cellular differentiation, including proliferation, adhesion, and control of cell morphology. Intriguing connections have also been made between PrPC and the modulation of circadian rhythm, glucose homeostasis, immune function and cellular iron uptake, all of which warrant further investigation.

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Overexpression of PrPc, combined with MGr1‐Ag/37LRP, is predictive of poor prognosis in gastric cancer

Cited by 38 publications

References 38 publications

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Down-regulation of LRIG1 by miR-20a modulates gastric cancer multidrug resistance

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

Physiological Functions of the Cellular Prion Protein

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