Cellular Prion Protein: History
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Subjects: Oncology
Contributor:
Gyeongyun Go
,
Sang Hun Lee

Studies on the cellular prion protein (PrPC) have been actively conducted because misfolded PrPC is known to cause transmissible spongiform encephalopathies or prion disease. PrPC is a glycophosphatidylinositol‐anchored cell surface glycoprotein that has been reported to affect several cellular functions such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation. Recently, it has also been reported that PrPC mediates tumor progression by enhancing the proliferation, metastasis, and drug resistance of cancer cells. In addition, PrPC regulates cancer stem cell properties by interacting with cancer stem cell marker proteins. In this review, we summarize how PrPC promotes tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties. In addition, we discuss strategies to treat tumors by modulating the function and expression of PrPC via the regulation of HSPA1L/HIF‐1α expression and using an anti‐prion antibody.

  • Cancer, PRNP, PrPC, prion protein,

1. Introduction

The cellular prion protein (PrPC) is a cell surface glycophosphatidylinositol (GPI)-anchored protein consisting of 208 amino acids, and it is encoded by the PRNP gene located on chromosome 20. PrPC has been intensively studied since it was proposed that misfolding of PrPC plays a key role in the pathogenesis of neurodegenerative diseases called transmissible spongiform encephalopathies [1][2][3]. Studies have shown that PrPC is not simply a cause of neurodegenerative diseases, but it is an important protein involved in many cellular functions such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation [4][5][6][7][8][9][10]. Furthermore, several studies have shown that PrPC expression is associated with tumor progression [11][12][13][14][15]. Before addressing the role of PrPC in tumor progression, we briefly introduce herein some biochemical aspects of PrPC.

PrPC is first synthesized as a precursor protein (pre-pro-PrP) comprising 253 amino acids with a signal peptide at the N-terminus and a GPI anchor peptide signaling sequence (GPI-PSS) at the C-terminus. The signal peptide directs pre-pro-PrP into the endoplasmic reticulum (ER), wherein it is cleaved to generate pro-PrP. The pro-PrP is then translocated from the ER to the Golgi complex [16][17] to be further processed by the addition of N-linked glycans, removal of the GPI-PSS, and addition of the pre-assembled GPI anchor [18][19]. Finally, the mature PrPC of 208 amino acids is translocated to the outer membrane leaflet of cells. However, not all PrPCs are present on the cell surface. They are constantly internalized through the recycling endosome and trafficked back repeatedly [20][21][22]. Through this recycling process, PrPCs are also found in the Golgi [22][23], in addition to the nucleus [24][25] and mitochondria [26][27].

The relationship between PrPC and cancer progression was first discovered when PRNP was identified as one of the most-expressed genes in pancreatic cancer cells [28]. Around the same time, other researchers found that PrPC was overexpressed in a drug-resistant cancer cell line compared to the parental cell line [29]. Based on several studies, it is now well established that PrPC is involved in the main aspects of cancer biology: proliferation, metastasis, and drug resistance. Moreover, the relationship between PrPC and cancer stem cell phenotypes has also been uncovered [30][31].

2. Overview of Physiological Functions of PrPC

PrPC is known to regulate several functions of cells, such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation. In this review, we briefly summarize the effects of PrPC on stress protection, cellular differentiation, and mitochondrial homeostasis.

Several studies have shown that PrPC can directly inhibit apoptosis. PrPC expression inhibited mitochondria-dependent apoptosis in Bax-overexpressing human primary neurons and MCF-7 breast cancer cells [32][33]. In addition, downregulation of PrPC reduced the viability of MDA-MB-435 breast cancer cells after serum deprivation [34]. In primary hippocampal neurons, PrPC protected the cells against staurosporine-induced cell death by interacting with stress-induced phosphoprotein 1 (STI1) [35][36][37]. PrPC is also known to protect cells from oxidative stress. For example, the basal levels of ROS and lipid peroxidation were lower in PrPC-transfected neuroblastoma and epithelial cell lines than in untransfected controls [38][39]. In addition, the expression of PrPC by primary neurons and astrocytes has been associated with lower levels of damage caused by the addition of various oxidative toxins such as xanthine oxidase, kainic acid, and hydrogen peroxide [40][41]. PrPC has also been found to be involved in the ER-stress response. When breast carcinoma cells were treated with the ER-stress inducing compounds such as brefeldin A, tunicamycin, and thapsigargin, the expression of PrPC was induced. Downregulation of PrPC in several cancer cell lines resulted in an increase in cell death in response to these toxins [13].

Neurite outgrowth is one of the characteristics of neuronal differentiation. Several studies have indicated that PrPC promotes neurite outgrowth through interactions with other proteins such as neural cell adhesion molecule 1, epidermal growth factor receptor, integrins, laminin, and STI1 [35][42][43][44][45]. The downstream signaling of these interactions may include RhoA-Rho kinase-LIMK-cofilin pathway [44]. Activation of various signal pathways, including extracellular signal-regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs), may also induce PrPC-dependent neurite outgrowth [35][43][46]. It has been reported that PrPC is also involved in the differentiation of embryonic stem cells. In human embryonic stem cells, downregulation of PrPC delays spontaneous differentiation into the three germ layers [47]. Similarly, PrPC expression promotes the differentiation of cultured human embryonic stem cells and multipotent neural precursors to mature neurons, astroglia, and oligodendroglia [47][48].

PrPC expression also affects mitochondrial homeostasis. Transcriptomic and proteomic analyses of brain tissues and neurons of PrPC-null and wild-type mice have identified differently expressed proteins. These proteins include cytochrome c oxidase subunits 1 and 2, which are involved in oxidative phosphorylation [49][50]. Furthermore, the absence of PrPC reduces the number of total mitochondria and increases the number of mitochondria with unusual morphology [49].

3. PrPC and Cancer Proliferation

PrPC expression has been reported to promote cancer proliferation in several types of cancer cells, including gastric [51], pancreatic [52], and colon [53][54][55], as well as in glioblastoma (GBM) [56][57] and schwannanoma [58].

In gastric cancer, PrPC promotes cell proliferation and metastasis of cancer cells and promotes tumor growth in xenograft mouse models [51]. PrPC increases the expression of cyclin D1 and thereby promotes their transition from the G0/G1 phase to the S-phase. PrPC expression also affects Akt signaling. Overexpression of PrPC increases p-Akt levels, whereas PrPC knockdown inhibits p-Akt expression [59]. Interestingly, it is known that certain regions of PrPC influence cell proliferation. Specifically, deletion of amino acids 24–50 of PrPC significantly reduced cell proliferation. Conversely, deletion of amino acids 51–91 did not affect apoptosis, metastasis cell proliferation, and multidrug resistance in gastric cancer [60].

In pancreatic ductal adenocarcinoma (PDAC), expression of PrPC increases the proliferation and migration of the cells. In PDAC cell lines, PrPC exists as a pro-PrP as it retains its GPI-PSS, which has a filamin A (FLNA) binding motif. It was found that the interaction between pro-PrP and FLNA, a cytoplasmic protein involved in actin organization, promotes cell migration [61]. In addition, other studies have shown that PrPC promote pancreatic cell proliferation by activating the Notch signaling pathway [62].

PrPC is known to interact with other membrane proteins or extracellular molecules to perform various cellular functions. In human GBM, PrPC and heat shock 90/70 organizing protein (HOP) are upregulated, and their expression levels correlate with higher proliferation rates and poorer clinical outcomes [56]. Additionally, it has been demonstrated that the binding of HOP to PrPC promotes proliferation of GBM cell lines and that disruption of PrPC–HOP interaction inhibits tumor growth and improves the survival of mice [56].

In DLS-1 and SW480 colorectal cancer cells, knockdown of PrPC significantly reduces the proliferation of cancer cells. It is known that the binding between HIF-2α and the GLUT1 promoter region decreases when PrPC expression is suppressed, resulting in a decrease in the expression of GLUT1. This may reduce glucose uptake and glycolysis and inhibit cell proliferation [54].

This entry is adapted from the peer-reviewed paper 10.3390/ijms21239208

References

  1. Prusiner, S.B. Novel proteinaceous infectious particles cause scrapie. Science 1982, 216, 136–144, doi:10.1126/science.6801762.
  2. Caughey, B.; Chesebro, B. Prion protein and the transmissible spongiform encephalopathies. Trends Cell Biol. 1997, 7, 56–62, doi:10.1016/S0962-8924(96)10054-4.
  3. Aguzzi, A.; Heppner, F.L. Pathogenesis of prion diseases: A progress report. Cell Death Differ. 2000, 7, 889–902, doi:10.1038/sj.cdd.4400737.
  4. Castle, A.R.; Gill, A.C. Physiological Functions of the Cellular Prion Protein. Mol. Biosci. 2017, 4, 19, doi:10.3389/fmolb.2017.00019.
  5. Dupiereux, I.; Falisse-Poirrier, N.; Zorzi, W.; Watt, N.T.; Thellin, O.; Zorzi, D.; Pierard, O.; Hooper, N.M.; Heinen, E.; Elmoualij, B. Protective effect of prion protein via the N-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells. Neurosci. Res. 2008, 86, 653–659, doi:10.1002/jnr.21506.
  6. Graner, E.; Mercadante, A.F.; Zanata, S.M.; Martins, V.R.; Jay, D.G.; Brentani, R.R. Laminin-induced PC-12 cell differentiation is inhibited following laser inactivation of cellular prion protein. FEBS Lett. 2000, 482, 257–260, doi:10.1016/s0014-5793(00)02070-6.
  7. Ramljak, S.; Asif, A.R.; Armstrong, V.W.; Wrede, A.; Groschup, M.H.; Buschmann, A.; Schulz-Schaeffer, W.; Bodemer, W.; Zerr, I. Physiological role of the cellular prion protein (PrPc): Protein profiling study in two cell culture systems. Proteome Res. 2008, 7, 2681–2695, doi:10.1021/pr7007187.
  8. Tobler, I.; Gaus, S.E.; Deboer, T.; Achermann, P.; Fischer, M.; Rulicke, T.; Moser, M.; Oesch, B.; McBride, P.A.; Manson, J.C. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 1996, 380, 639–642, doi:10.1038/380639a0.
  9. Bremer, J.; Baumann, F.; Tiberi, C.; Wessig, C.; Fischer, H.; Schwarz, P.; Steele, A.D.; Toyka, K.V.; Nave, K.A.; Weis, J.; et al. Axonal prion protein is required for peripheral myelin maintenance. Neurosci. 2010, 13, 310–318, doi:10.1038/nn.2483.
  10. Haddon, D.J.; Hughes, M.R.; Antignano, F.; Westaway, D.; Cashman, N.R.; McNagny, K.M. Prion protein expression and release by mast cells after activation. Infect. Dis 2009, 200, 827–831, doi:10.1086/605022.
  11. Santos, T.G.; Lopes, M.H.; Martins, V.R. Targeting prion protein interactions in cancer. Prion 2015, 9, 165–173, doi:10.1080/19336896.2015.1027855.
  12. Gao, Z.; Peng, M.; Chen, L.; Yang, X.; Li, H.; Shi, R.; Wu, G.; Cai, L.; Song, Q.; Li, C. Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis. Sin. 2019, 34, 222–234, doi:10.1007/s12250-019-00107-2.
  13. Dery, M.A.; Jodoin, J.; Ursini-Siegel, J.; Aleynikova, O.; Ferrario, C.; Hassan, S.; Basik, M.; LeBlanc, A.C. Endoplasmic reticulum stress induces PRNP prion protein gene expression in breast cancer. Breast Cancer Res. 2013, 15, R22, doi:10.1186/bcr3398.
  14. Mehrpour, M.; Codogno, P. Prion protein: From physiology to cancer biology. Cancer Lett. 2010, 290, 1–23, doi:10.1016/j.canlet.2009.07.009.
  15. Tang, Z.; Ma, J.; Zhang, W.; Gong, C.; He, J.; Wang, Y.; Yu, G.; Yuan, C.; Wang, X.; Sun, Y.; et al. The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis. Cancer 2016, 7, 984–990, doi:10.7150/jca.14237.
  16. Tanaka, S.; Maeda, Y.; Tashima, Y.; Kinoshita, T. Inositol deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p. Biol. Chem. 2004, 279, 14256–14263, doi:10.1074/jbc.M313755200.
  17. Bonnon, C.; Wendeler, M.W.; Paccaud, J.P.; Hauri, H.P. Selective export of human GPI-anchored proteins from the endoplasmic reticulum. Cell Sci. 2010, 123, 1705–1715, doi:10.1242/jcs.062950.
  18. Sarnataro, D.; Campana, V.; Paladino, S.; Stornaiuolo, M.; Nitsch, L.; Zurzolo, C. PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. Biol. Cell 2004, 15, 4031–4042, doi:10.1091/mbc.e03-05-0271.
  19. Campana, V.; Sarnataro, D.; Zurzolo, C. The highways and byways of prion protein trafficking. Trends Cell Biol. 2005, 15, 102–111, doi:10.1016/j.tcb.2004.12.002.
  20. Shyng, S.L.; Huber, M.T.; Harris, D.A. A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. Biol. Chem. 1993, 268, 15922–15928.
  21. Sunyach, C.; Jen, A.; Deng, J.; Fitzgerald, K.T.; Frobert, Y.; Grassi, J.; McCaffrey, M.W.; Morris, R. The mechanism of internalization of glycosylphosphatidylinositol-anchored prion protein. EMBO J. 2003, 22, 3591–3601, doi:10.1093/emboj/cdg344.
  22. Magalhaes, A.C.; Silva, J.A.; Lee, K.S.; Martins, V.R.; Prado, V.F.; Ferguson, S.S.; Gomez, M.V.; Brentani, R.R.; Prado, M.A. Endocytic intermediates involved with the intracellular trafficking of a fluorescent cellular prion protein. Biol. Chem. 2002, 277, 33311–33318, doi:10.1074/jbc.M203661200.
  23. Lee, K.S.; Magalhaes, A.C.; Zanata, S.M.; Brentani, R.R.; Martins, V.R.; Prado, M.A. Internalization of mammalian fluorescent cellular prion protein and N-terminal deletion mutants in living cells. Neurochem. 2001, 79, 79–87, doi:10.1046/j.1471-4159.2001.00529.x.
  24. Gu, Y.; Hinnerwisch, J.; Fredricks, R.; Kalepu, S.; Mishra, R.S.; Singh, N. Identification of cryptic nuclear localization signals in the prion protein. Dis. 2003, 12, 133–149, doi:10.1016/s0969-9961(02)00014-1.
  25. Morel, E.; Fouquet, S.; Strup-Perrot, C.; Pichol Thievend, C.; Petit, C.; Loew, D.; Faussat, A.M.; Yvernault, L.; Pincon-Raymond, M.; Chambaz, J.; et al. The cellular prion protein PrP(c) is involved in the proliferation of epithelial cells and in the distribution of junction-associated proteins. PLoS ONE 2008, 3, e3000, doi:10.1371/journal.pone.0003000.
  26. Hachiya, N.S.; Yamada, M.; Watanabe, K.; Jozuka, A.; Ohkubo, T.; Sano, K.; Takeuchi, Y.; Kozuka, Y.; Sakasegawa, Y.; Kaneko, K. Mitochondrial localization of cellular prion protein (PrPC) invokes neuronal apoptosis in aged transgenic mice overexpressing PrPC. Lett. 2005, 374, 98–103, doi:10.1016/j.neulet.2004.10.044.
  27. Satoh, J.; Onoue, H.; Arima, K.; Yamamura, T. The 14-3-3 protein forms a molecular complex with heat shock protein Hsp60 and cellular prion protein. Neuropathol. Exp. Neurol 2005, 64, 858–868, doi:10.1097/01.jnen.0000182979.56612.08.
  28. Han, H.; Bearss, D.J.; Browne, L.W.; Calaluce, R.; Nagle, R.B.; Von Hoff, D.D. Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res. 2002, 62, 2890–2896.
  29. Zhao, Y.; You, H.; Liu, F.; An, H.; Shi, Y.; Yu, Q.; Fan, D. Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. Cancer Lett. 2002, 185, 211–218, doi:10.1016/s0304-3835(02)00264-1.
  30. Domingues, P.H.; Nanduri, L.S.Y.; Seget, K.; Venkateswaran, S.V.; Agorku, D.; Vigano, C.; von Schubert, C.; Nigg, E.A.; Swanton, C.; Sotillo, R.; et al. Cellular Prion Protein PrP(C) and Ecto-5'-Nucleotidase Are Markers of the Cellular Stress Response to Aneuploidy. Cancer Res. 2017, 77, 2914–2926, doi:10.1158/0008-5472.CAN-16-3052.
  31. Lee, J.H.; Yun, C.W.; Han, Y.S.; Kim, S.; Jeong, D.; Kwon, H.Y.; Kim, H.; Baek, M.J.; Lee, S.H. Melatonin and 5-fluorouracil co-suppress colon cancer stem cells by regulating cellular prion protein-Oct4 axis. Pineal. Res. 2018, 65, e12519, doi:10.1111/jpi.12519.
  32. Bounhar, Y.; Zhang, Y.; Goodyer, C.G.; LeBlanc, A. Prion protein protects human neurons against Bax-mediated apoptosis. Biol. Chem. 2001, 276, 39145–39149, doi:10.1074/jbc.C100443200.
  33. Roucou, X.; Giannopoulos, P.N.; Zhang, Y.; Jodoin, J.; Goodyer, C.G.; LeBlanc, A. Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells. Cell Death Differ. 2005, 12, 783–795, doi:10.1038/sj.cdd.4401629.
  34. Yu, G.; Jiang, L.; Xu, Y.; Guo, H.; Liu, H.; Zhang, Y.; Yang, H.; Yuan, C.; Ma, J. Silencing prion protein in MDA-MB-435 breast cancer cells leads to pleiotropic cellular responses to cytotoxic stimuli. PLoS ONE 2012, 7, e48146, doi:10.1371/journal.pone.0048146.
  35. Lopes, M.H.; Hajj, G.N.; Muras, A.G.; Mancini, G.L.; Castro, R.M.; Ribeiro, K.C.; Brentani, R.R.; Linden, R.; Martins, V.R. Interaction of cellular prion and stress-inducible protein 1 promotes neuritogenesis and neuroprotection by distinct signaling pathways. Neurosci. 2005, 25, 11330–11339, doi:10.1523/JNEUROSCI.2313-05.2005.
  36. Beraldo, F.H.; Arantes, C.P.; Santos, T.G.; Queiroz, N.G.; Young, K.; Rylett, R.J.; Markus, R.P.; Prado, M.A.; Martins, V.R. Role of alpha7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress-inducible protein 1. Biol. Chem. 2010, 285, 36542–36550, doi:10.1074/jbc.M110.157263.
  37. Ostapchenko, V.G.; Beraldo, F.H.; Mohammad, A.H.; Xie, Y.F.; Hirata, P.H.; Magalhaes, A.C.; Lamour, G.; Li, H.; Maciejewski, A.; Belrose, J.C.; et al. The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid-beta oligomer toxicity. Neurosci. 2013, 33, 16552–16564, doi:10.1523/JNEUROSCI.3214-13.2013.
  38. Rachidi, W.; Vilette, D.; Guiraud, P.; Arlotto, M.; Riondel, J.; Laude, H.; Lehmann, S.; Favier, A. Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery. Biol. Chem. 2003, 278, 9064–9072, doi:10.1074/jbc.M211830200.
  39. Zeng, F.; Watt, N.T.; Walmsley, A.R.; Hooper, N.M. Tethering the N-terminus of the prion protein compromises the cellular response to oxidative stress. Neurochem. 2003, 84, 480–490, doi:10.1046/j.1471-4159.2003.01529.x.
  40. Brown, D.R.; Nicholas, R.S.; Canevari, L. Lack of prion protein expression results in a neuronal phenotype sensitive to stress. Neurosci. Res. 2002, 67, 211–224, doi:10.1002/jnr.10118.
  41. Anantharam, V.; Kanthasamy, A.; Choi, C.J.; Martin, D.P.; Latchoumycandane, C.; Richt, J.A.; Kanthasamy, A.G. Opposing roles of prion protein in oxidative stress- and ER stress-induced apoptotic signaling. Free Radic. Biol. Med. 2008, 45, 1530–1541, doi:10.1016/j.freeradbiomed.2008.08.028.
  42. Santuccione, A.; Sytnyk, V.; Leshchyns'ka, I.; Schachner, M. Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. Cell Biol. 2005, 169, 341–354, doi:10.1083/jcb.200409127.
  43. Llorens, F.; Carulla, P.; Villa, A.; Torres, J.M.; Fortes, P.; Ferrer, I.; del Rio, J.A. PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells. Neurochem. 2013, 127, 124–138, doi:10.1111/jnc.12283.
  44. Loubet, D.; Dakowski, C.; Pietri, M.; Pradines, E.; Bernard, S.; Callebert, J.; Ardila-Osorio, H.; Mouillet-Richard, S.; Launay, J.M.; Kellermann, O.; et al. Neuritogenesis: The prion protein controls beta1 integrin signaling activity. FASEB J. 2012, 26, 678–690, doi:10.1096/fj.11-185579.
  45. Graner, E.; Mercadante, A.F.; Zanata, S.M.; Forlenza, O.V.; Cabral, A.L.; Veiga, S.S.; Juliano, M.A.; Roesler, R.; Walz, R.; Minetti, A.; et al. Cellular prion protein binds laminin and mediates neuritogenesis. Brain Res. Mol. Brain Res. 2000, 76, 85–92, doi:10.1016/s0169-328x(99)00334-4.
  46. Caetano, F.A.; Lopes, M.H.; Hajj, G.N.; Machado, C.F.; Pinto Arantes, C.; Magalhaes, A.C.; Vieira Mde, P.; Americo, T.A.; Massensini, A.R.; Priola, S.A.; et al. Endocytosis of prion protein is required for ERK1/2 signaling induced by stress-inducible protein 1. Neurosci. 2008, 28, 6691–6702, doi:10.1523/JNEUROSCI.1701-08.2008.
  47. Lee, Y.J.; Baskakov, I.V. The cellular form of the prion protein guides the differentiation of human embryonic stem cells into neuron-, oligodendrocyte-, and astrocyte-committed lineages. Prion 2014, 8, 266–275, doi:10.4161/pri.32079.
  48. Steele, A.D.; Emsley, J.G.; Ozdinler, P.H.; Lindquist, S.; Macklis, J.D. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Natl. Acad. Sci. USA 2006, 103, 3416–3421, doi:10.1073/pnas.0511290103.
  49. Miele, G.; Jeffrey, M.; Turnbull, D.; Manson, J.; Clinton, M. Ablation of cellular prion protein expression affects mitochondrial numbers and morphology. Biophys. Res. Commun. 2002, 291, 372–377, doi:10.1006/bbrc.2002.6460.
  50. Stella, R.; Cifani, P.; Peggion, C.; Hansson, K.; Lazzari, C.; Bendz, M.; Levander, F.; Sorgato, M.C.; Bertoli, A.; James, P. Relative quantification of membrane proteins in wild-type and prion protein (PrP)-knockout cerebellar granule neurons. Proteome Res. 2012, 11, 523–536, doi:10.1021/pr200759m.
  51. Liang, J.; Luo, G.; Ning, X.; Shi, Y.; Zhai, H.; Sun, S.; Jin, H.; Liu, Z.; Zhang, F.; Lu, Y.; et al. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Cell Biol. 2007, 85, 375–383, doi:10.1139/o07-052.
  52. Li, Q.Q.; Cao, X.X.; Xu, J.D.; Chen, Q.; Wang, W.J.; Tang, F.; Chen, Z.Q.; Liu, X.P.; Xu, Z.D. The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel. Cell Mol. Life Sci. 2009, 66, 504–515, doi:10.1007/s00018-008-8548-6.
  53. Le Corre, D.; Ghazi, A.; Balogoun, R.; Pilati, C.; Aparicio, T.; Martin-Lanneree, S.; Marisa, L.; Djouadi, F.; Poindessous, V.; Crozet, C.; et al. The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer. EBioMedicine 2019, 46, 94–104, doi:10.1016/j.ebiom.2019.07.036.
  54. Li, Q.Q.; Sun, Y.P.; Ruan, C.P.; Xu, X.Y.; Ge, J.H.; He, J.; Xu, Z.D.; Wang, Q.; Gao, W.C. Cellular prion protein promotes glucose uptake through the Fyn-HIF-2alpha-Glut1 pathway to support colorectal cancer cell survival. Cancer Sci. 2011, 102, 400–406, doi:10.1111/j.1349-7006.2010.01811.x.
  55. Chieng, C.K.; Say, Y.H. Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by increasing invasiveness and resistance against doxorubicin-induced apoptosis. Biol. 2015, 36, 8107–8120, doi:10.1007/s13277-015-3530-z.
  56. Lopes, M.H.; Santos, T.G.; Rodrigues, B.R.; Queiroz-Hazarbassanov, N.; Cunha, I.W.; Wasilewska-Sampaio, A.P.; Costa-Silva, B.; Marchi, F.A.; Bleggi-Torres, L.F.; Sanematsu, P.I.; et al. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. Oncogene 2015, 34, 3305–3314, doi:10.1038/onc.2014.261.
  57. Corsaro, A.; Bajetto, A.; Thellung, S.; Begani, G.; Villa, V.; Nizzari, M.; Pattarozzi, A.; Solari, A.; Gatti, M.; Pagano, A.; et al. Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells. Oncotarget 2016, 7, 38638–38657, doi:10.18632/oncotarget.9575.
  58. Provenzano, L.; Ryan, Y.; Hilton, D.A.; Lyons-Rimmer, J.; Dave, F.; Maze, E.A.; Adams, C.L.; Rigby-Jones, R.; Ammoun, S.; Hanemann, C.O. Cellular prion protein (PrP(C)) in the development of Merlin-deficient tumours. Oncogene 2017, 36, 6132–6142, doi:10.1038/onc.2017.200.
  59. Liang, J.; Ge, F.; Guo, C.; Luo, G.; Wang, X.; Han, G.; Zhang, D.; Wang, J.; Li, K.; Pan, Y.; et al. Inhibition of PI3K/Akt partially leads to the inhibition of PrP(C)-induced drug resistance in gastric cancer cells. FEBS J. 2009, 276, 685–694, doi:10.1111/j.1742-4658.2008.06816.x.
  60. Liang, J.; Wang, J.; Luo, G.; Pan, Y.; Wang, X.; Guo, C.; Zhang, D.; Yin, F.; Zhang, X.; Liu, J.; et al. Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines. Cell Mol. Med. 2009, 13, 4453–4464, doi:10.1111/j.1582-4934.2009.00687.x.
  61. Li, C.; Xin, W.; Sy, M.S. Binding of pro-prion to filamin A: By design or an unfortunate blunder. Oncogene 2010, 29, 5329–5345, doi:10.1038/onc.2010.307.
  62. Wang, Y.; Yu, S.; Huang, D.; Cui, M.; Hu, H.; Zhang, L.; Wang, W.; Parameswaran, N.; Jackson, M.; Osborne, B.; et al. Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1. J. Pathol. 2016, 186, 2945–2956, doi:10.1016/j.ajpath.2016.07.010.
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