The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel

Li, Q.-Q.; Cao, Xi-Xi; Xu, Junji; Chen, Q.; Wang, W.-J.; Tang, Feng; Chen, Z.-Q.; Liu, X.-P.; Xu, Zu-De

doi:10.1007/s00018-008-8548-6

Cited by 44 publications

(56 citation statements)

References 30 publications

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“…Previous studies on PrP c in cancer are generally consistent with the notion that PrP c expression increases resistance to cytotoxicity (27)(28)(29)(30)(31). One of the ways to eliminate this is via inhibition of glucose by various therapeutic drugs (32).…”

Section: Effect Of Fucoidan On Ht29 Colon Cancer Cell Apoptosis Htmentioning

confidence: 52%

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan

Yun

Lee

et al. 2016

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Developing natural products and dietary supplements has proven to be a promising strategy for the cancer therapy and prevention. Among them, fucoidan, which is isolated from brown seaweed such as Cladosiphon okamuranus and Fucus evanescens (1, 2), is structurally similar to heparin, with a substantial percentage of L-fucose (3, 4). Recent studies have shown its various effects on biological activities such as antiinflammatory, anti-coagulant (5), anti-HIV, and anticancer (6-9) activities. With respect to cancer therapy, fucoidan appears to be highly efficient in treating certain types of cancer, including breast, prostate and lung, as well as leukemia (10-12). Furthermore, fucoidan can also play a crucial role in inhibiting induced cancer signaling molecules, such as vascular endothelial growth factor (VEGF) (13,14). Although these results support the potential development of fucoidan as an anticancer drug, there is little information on the anticancer effect of fucoidan on colorectal cancer (CRC).CRC is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite continuous progress in developing diagnostic and therapeutic methods (15). It is thought that CRC may be caused by a combination of both genetic susceptibilities and Iifestyle factors such as a meat-rich diet (16). Although the discovery of factors that cause CRC give new insights into the growth and metastasis of CRC, there is still little information on the etiology of most CRC, therapeutic agents, and anti-CRC targeting molecules. However, cellular prion protein (PrP c ) expression has been identified as a risk or susceptibility factor for developing CRC (17). In essence, PrP c is a highly conserved cell-surface glycoprotein that has been identified in all vertebrates, with the same protein sequence as the prion proteins that cause 4449

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Section: Effect Of Fucoidan On Ht29 Colon Cancer Cell Apoptosis Htmentioning

confidence: 52%

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan

Yun

Lee

et al. 2016

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“…The molecular mechanism of multi-drug resistance (MDR) in cancer cells has long been associated with P-glycoprotein, an energy-dependent multi-drug efflux pump (reviewed in [154]). Recently, it was shown that PrP interacts with P-glycoprotein and is essential for drug resistance in breast cancer cells [155]. Several studies have also functionally linked MDR and tumor metastasis [156–159].…”

Section: Implications For Prevention Early Diagnosis and Targeted Tmentioning

confidence: 99%

Potential roles for prions and protein-only inheritance in cancer

Antony

Wiegmans

Wei

et al. 2011

Cancer Metastasis Rev

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Inherited mutations are known to cause familial cancers. However, the cause of sporadic cancers, which likely represent the majority of cancers, is yet to be elucidated. Sporadic cancers contain somatic mutations (including oncogenic mutations), however, the origin of these mutations is unclear. An intriguing possibility is that a stable alteration occurs in somatic cells prior to oncogenic mutations and promotes the subsequent accumulation of oncogenic mutations. This review explores the possible role of prions and protein-only inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast, have identified a large number of proteins as prions that confer dominant phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have mammalian functional homologs. The human prion protein (PrP) is known to cause neurodegenerative diseases and has now been found to be up-regulated in multiple cancers. PrP expression in cancer cells contributes to cancer progression and resistance to various cancer therapies. Epigenetic changes in gene expression and hyper-activation of MAP kinase (MAPK) signalling, processes that in lower eukaryotes are affected by prions, play important roles in oncogenesis in humans. Prion phenomena in yeast appear to be influenced by stresses and there is considerable evidence for association of some amyloids with biologically positive functions. This suggests that if protein-only somatic inheritance exists in mammalian cells, it might contribute to cancer phenotypes. Here we highlight evidence in the literature for an involvement of prion or prion-like mechanisms in cancer and how they may in the future be viewed as diagnostic markers and potential therapeutic targets.

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“…Both PrP C and HOP also modulate tumorigenesis, affecting the progression and maintenance of different types of cancers [8]. PrP C associates with a poor clinical outcome and survival in pancreatic ductal adenocarcinoma and melanoma [9, 10], and with invasion and metastasis in gastric and breast cancers [8, 11, 12]. Depleting PrP C inhibits growth, promotes programmed cell death in gliomas [13], and sensitizes tumor cells to cytotoxic drugs [14].…”

Section: Introductionmentioning

confidence: 99%

Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells

Iglesia¹,

Prado

Cruz

et al. 2017

Stem Cell Res Ther

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BackgroundGlioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrPC) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance.MethodsGSCs expressing different levels of PrPC were cultured as neurospheres with growth factors, and characterized with stem cells markers and adhesion molecules markers through immunofluorescence and flow cytometry. We than evaluated GSC self-renewal and proliferation by clonal density assays and BrdU incorporation, respectively, in front of recombinant HOP treatment, combined or not with a HOP peptide which mimics the PrPC binding site. Stable silencing of HOP was also performed in parental and/or PrPC-depleted cell populations, and proliferation in vitro and tumor growth in vivo were evaluated. Migration assays were performed on laminin-1 pre-coated glass.ResultsWe observed that, when GBM cells are cultured as neurospheres, they express specific stemness markers such as CD133, CD15, Oct4, and SOX2; PrPC is upregulated compared to monolayer culture and co-localizes with CD133. PrPC silencing downregulates the expression of molecules associated with cancer stem cells, upregulates markers of cell differentiation and affects GSC self-renewal, pointing to a pivotal role for PrPC in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and self-renewal of GSCs in a PrPC-dependent manner while HOP knockdown disturbs the proliferation process. In vivo, PrPC and/or HOP knockdown potently inhibits the growth of subcutaneously implanted glioblastoma cells. In addition, disruption of the PrPC-HOP complex by a HOP peptide, which mimics the PrPC binding site, affects GSC self-renewal and proliferation indicating that the HOP-PrPC complex is required for GSC stemness. Furthermore, PrPC-depleted GSCs downregulate cell adhesion-related proteins and impair cell migration indicating a putative role for PrPC in the cell surface stability of cell adhesion molecules and GBM cell invasiveness, respectively.ConclusionsIn conclusion, our results show that the modulation of HOP-PrPC engagement or the decrease of PrPC and HOP expression may represent a potential therapeutic intervention in GBM, regulating glioblastoma stem-like cell self-renewal, proliferation, and migration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0518-1) contains supplementary material, which is available to authorized users.

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The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel

Cited by 44 publications

References 30 publications

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan

Potential roles for prions and protein-only inheritance in cancer

Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells

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