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Vai trò của protein tiếp nhận liên quan đến lipoprotein tỷ trọng thấp 1 trong các khối u
Tóm tắt
Protein tiếp nhận liên quan đến lipoprotein tỷ trọng thấp 1 (LRP1, còn được biết đến với tên CD91), là một protein tiếp nhận đa chức năng tham gia vào quá trình nội bào và truyền tín hiệu tế bào, được biểu hiện rộng rãi trên bề mặt của nhiều loại tế bào như tế bào gan, tế bào nguyên bào sợi, tế bào thần kinh, tế bào sao, đại thực bào, tế bào cơ trơn và tế bào ác tính. Bằng chứng đang nổi lên từ các nghiên cứu in vitro và in vivo cho thấy LRP1 có vai trò quan trọng trong nhiều quá trình thúc đẩy sự hình thành và tiến triển của khối u. Ví dụ, LRP1 không chỉ thúc đẩy sự di động và xâm lấn của tế bào khối u bằng cách điều chỉnh sự biểu hiện và chức năng của protease làm mềm mô (MMP)-2 và MMP-9, mà còn ức chế sự apoptosis của tế bào bằng cách điều chỉnh thụ thể insulin, con đường tín hiệu protein kinase serine/threonine, và sự biểu hiện của Caspase-3. Sự phosphoryl hóa thông qua LRP1 của con đường kinase điều chỉnh tín hiệu ngoại bào và kinase N-terminal c-jun cũng liên quan đến sự tăng sinh và xâm lấn của tế bào khối u. Ngoài ra, LRP1 đã được chứng minh là bị giảm điều hòa bởi microRNA-205 và sự methyl hóa các đảo CpG của LRP1. Hơn nữa, một gen liên hợp mới, LRP1-SNRNP25, thúc đẩy sự xâm lấn và di chuyển của tế bào u xương. Chỉ khi hiểu được các cơ chế của những tác động này, chúng ta mới có thể phát triển các chiến lược chẩn đoán và điều trị mới cho các loại ung thư được trung gian bởi LRP1.
Từ khóa
#LRP1 #khối u #di động tế bào #xâm lấn tế bào #apoptosis #methyl hóa #microRNATài liệu tham khảo
Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK. Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J. 1988;7(13):4119–27.
Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest. 2001;108(6):779–84. doi:10.1172/jci13992.
Kang HS, Kim J, Lee HJ, Kwon BM, Lee DK, Hong SH. LRP1-dependent pepsin clearance induced by 2′-hydroxycinnamaldehyde attenuates breast cancer cell invasion. Int J Biochem Cell Biol. 2014;53:15–23. doi:10.1016/j.biocel.2014.04.021.
Muratoglu SC, Mikhailenko I, Newton C, Migliorini M, Strickland DK. Low density lipoprotein receptor-related protein 1 (LRP1) forms a signaling complex with platelet-derived growth factor receptor-beta in endosomes and regulates activation of the MAPK pathway. J Biol Chem. 2010;285(19):14308–17. doi:10.1074/jbc.M109.046672.
Mantuano E, Lam MS, Gonias SL. LRP1 assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein. J Biol Chem. 2013;288(47):34009–18. doi:10.1074/jbc.M113.509133.
Kasza A, Petersen HH, Heegaard CW, Oka K, Christensen A, Dubin A, et al. Specificity of serine proteinase/serpin complex binding to very-low-density lipoprotein receptor and alpha2-macroglobulin receptor/low-density-lipoprotein-receptor-related protein. Eur J Biochem. 1997;248(2):270–81.
Roura S, Cal R, Galvez-Monton C, Revuelta-Lopez E, Nasarre L, Badimon L, et al. Inverse relationship between raft LRP1 localization and non-raft ERK1,2/MMP9 activation in idiopathic dilated cardiomyopathy: potential impact in ventricular remodeling. Int J Cardiol. 2014;176(3):805–14. doi:10.1016/j.ijcard.2014.07.270.
Fuentealba RA, Liu Q, Kanekiyo T, Zhang J, Bu G. Low density lipoprotein receptor-related protein 1 promotes anti-apoptotic signaling in neurons by activating Akt survival pathway. J Biol Chem. 2009;284(49):34045–53. doi:10.1074/jbc.M109.021030.
Schneider WJ, Nimpf J. LDL receptor relatives at the crossroad of endocytosis and signaling. Cell Mol Life Sci. 2003;60(5):892–903. doi:10.1007/s00018-003-2183-Z.
Boucher P, Herz J. Signaling through LRP1: protection from atherosclerosis and beyond. Biochem Pharmacol. 2011;81(1):1–5. doi:10.1016/j.bcp.2010.09.018.
Neels JG, van Den Berg BM, Lookene A, Olivecrona G, Pannekoek H, van Zonneveld AJ. The second and fourth cluster of class A cysteine-rich repeats of the low density lipoprotein receptor-related protein share ligand-binding properties. J Biol Chem. 1999;274(44):31305–11.
Kanekiyo T, Bu G. The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer’s disease. Front Aging Neurosci. 2014;6:93. doi:10.3389/fnagi.2014.00093.
Li Y, Marzolo MP, van Kerkhof P, Strous GJ, Bu G. The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor-related protein. J Biol Chem. 2000;275(22):17187–94. doi:10.1074/jbc.M000490200.
Li Y, Lu W, Marzolo MP, Bu G. Differential functions of members of the low density lipoprotein receptor family suggested by their distinct endocytosis rates. J Biol Chem. 2001;276(21):18000–6. doi:10.1074/jbc.M101589200.
von Arnim CA, Kinoshita A, Peltan ID, Tangredi MM, Herl L, Lee BM, et al. The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. J Biol Chem. 2005;280(18):17777–85. doi:10.1074/jbc.M414248200.
Weaver AM, Hussaini IM, Mazar A, Henkin J, Gonias SL. Embryonic fibroblasts that are genetically deficient in low density lipoprotein receptor-related protein demonstrate increased activity of the urokinase receptor system and accelerated migration on vitronectin. J Biol Chem. 1997;272(22):14372–9.
Langlois B, Perrot G, Schneider C, Henriet P, Emonard H, Martiny L, et al. LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways. PLoS One. 2010;5(7):e11584. doi:10.1371/journal.pone.0011584.
Benes P, Jurajda M, Zaloudik J, Izakovicova-Holla L, Vacha J. C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer. Breast Cancer Res. 2003;5(3):R77–81. doi:10.1186/bcr591.
Baum L, Dong ZY, Choy KW, Pang CP, Ng HK. Low density lipoprotein receptor related protein gene amplification and 766T polymorphism in astrocytomas. Neurosci Lett. 1998;256(1):5–8.
Gopal U, Bohonowych JE, Lema-Tome C, Liu A, Garrett-Mayer E, Wang B, et al. A novel extracellular Hsp90 mediated co-receptor function for LRP1 regulates EphA2 dependent glioblastoma cell invasion. PLoS One. 2011;6(3):e17649. doi:10.1371/journal.pone.0017649.
Catasus L, Llorente-Cortes V, Cuatrecasas M, Pons C, Espinosa I, Prat J. Low-density lipoprotein receptor-related protein 1 (LRP-1) is associated with highgrade, advanced stage and p53 and p16 alterations in endometrial carcinomas. Histopathology. 2011;59(3):567–71. doi:10.1111/j.1365-2559.2011.03942.x.
Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64(2):327–36.
Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89(17):1260–70.
Wang M, Wang T, Liu S, Yoshida D, Teramoto A. The expression of matrix metalloproteinase-2 and -9 in human gliomas of different pathological grades. Brain Tumor Pathol. 2003;20(2):65–72.
Song H, Li Y, Lee J, Schwartz AL, Bu G. Low-density lipoprotein receptor-related protein 1 promotes cancer cell migration and invasion by inducing the expression of matrix metalloproteinases 2 and 9. Cancer Res. 2009;69(3):879–86. doi:10.1158/0008-5472.can-08-3379.
Fink K, Boratynski J. The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis. Postepy Hig Med Dosw (Online). 2012;66:609–28 [in Polish].
Hu K, Yang J, Tanaka S, Gonias SL, Mars WM, Liu Y. Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression. J Biol Chem. 2006;281(4):2120–7. doi:10.1074/jbc.M504988200.
Fayard B, Bianchi F, Dey J, Moreno E, Djaffer S, Hynes NE, et al. The serine protease inhibitor protease nexin-1 controls mammary cancer metastasis through LRP-1-mediated MMP-9 expression. Cancer Res. 2009;69(14):5690–8. doi:10.1158/0008-5472.can-08-4573.
Barcelona PF, Jaldin-Fincati JR, Sanchez MC, Chiabrando GA. Activated alpha2-macroglobulin induces Muller glial cell migration by regulating MT1-MMP activity through LRP1. Faseb J. 2013;27(8):3181–97. doi:10.1096/fj.12-221598.
Athauda SB, Nishigai M, Arakawa H, Ikai A, Ukai M, Takahashi K. Inhibition of human pepsin and gastricsin by alpha2-macroglobulin. J Enzyme Inhib Med Chem. 2003;18(3):219–24.
Johnston N, Yan JC, Hoekzema CR, Samuels TL, Stoner GD, Blumin JH, et al. Pepsin promotes proliferation of laryngeal and pharyngeal epithelial cells. Laryngoscope. 2012;122(6):1317–25. doi:10.1002/lary.23307.
Mantuano E, Inoue G, Li X, Takahashi K, Gaultier A, Gonias SL, et al. The hemopexin domain of matrix metalloproteinase-9 activates cell signaling and promotes migration of schwann cells by binding to low-density lipoprotein receptor-related protein. J Neurosci. 2008;28(45):11571–82. doi:10.1523/jneurosci.3053-08.2008.
Takayama Y, Takahashi H, Mizumachi K, Takezawa T. Low density lipoprotein receptor-related protein (LRP) is required for lactoferrin-enhanced collagen gel contractile activity of human fibroblasts. J Biol Chem. 2003;278(24):22112–8. doi:10.1074/jbc.M300894200.
Montel V, Gaultier A, Lester RD, Campana WM, Gonias SL. The low-density lipoprotein receptor-related protein regulates cancer cell survival and metastasis development. Cancer Res. 2007;67(20):9817–24. doi:10.1158/0008-5472.can-07-0683.
Sidenius N, Blasi F. The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy. Cancer Metastasis Rev. 2003;22(2–3):205–22.
Sid B, Dedieu S, Delorme N, Sartelet H, Rath GM, Bellon G, et al. Human thyroid carcinoma cell invasion is controlled by the low density lipoprotein receptor-related protein-mediated clearance of urokinase plasminogen activator. Int J Biochem Cell Biol. 2006;38(10):1729–40. doi:10.1016/j.biocel.2006.04.005.
Huang XY, Shi GM, Devbhandari RP, Ke AW, Wang Y, Wang XY, et al. Low level of low-density lipoprotein receptor-related protein 1 predicts an unfavorable prognosis of hepatocellular carcinoma after curative resection. PLoS One. 2012;7(3):e32775. doi:10.1371/journal.pone.0032775.
Foca C, Moses EK, Quinn MA, Rice GE. Differential expression of the alpha(2)-macroglobulin receptor and the receptor associated protein in normal human endometrium and endometrial carcinoma. Mol Hum Reprod. 2000;6(10):921–7.
Kancha RK, Stearns ME, Hussain MM. Decreased expression of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor in invasive cell clones derived from human prostate and breast tumor cells. Oncol Res. 1994;6(8):365–72.
Meng H, Chen G, Zhang X, Wang Z, Thomas DG, Giordano TJ, et al. Stromal LRP1 in lung adenocarcinoma predicts clinical outcome. Clin Cancer Res. 2011;17(8):2426–33. doi:10.1158/1078-0432.ccr-10-2385.
Desrosiers RR, Rivard ME, Grundy PE, Annabi B. Decrease in LDL receptor-related protein expression and function correlates with advanced stages of Wilms tumors. Pediatr Blood Cancer. 2006;46(1):40–9. doi:10.1002/pbc.20566.
Laoui D, Movahedi K, Van Overmeire E, Van den Bossche J, Schouppe E, Mommer C, et al. Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions. Int J Dev Biol. 2011;55(7–9):861–7. doi:10.1387/ijdb.113371dl.
Zhang BC, Gao J, Wang J, Rao ZG, Wang BC, Gao JF. Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma. Med Oncol. 2011;28(4):1447–52. doi:10.1007/s12032-010-9638-5.
Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317(5834):121–4. doi:10.1126/science.1140485.
Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–51. doi:10.1016/j.cell.2010.03.014.
Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64(19):7022–9. doi:10.1158/0008-5472.can-04-1449.
Staudt ND, Jo M, Hu J, Bristow JM, Pizzo DP, Gaultier A, et al. Myeloid cell receptor LRP1/CD91 regulates monocyte recruitment and angiogenesis in tumors. Cancer Res. 2013;73(13):3902–12. doi:10.1158/0008-5472.can-12-4233.
Qu Y, Dang S, Hou P. Gene methylation in gastric cancer. Clin Chim Acta. 2013;424:53–65. doi:10.1016/j.cca.2013.05.002.
Ehrlich M, Jiang G, Fiala E, Dome JS, Yu MC, Long TI, et al. Hypomethylation and hypermethylation of DNA in Wilms tumors. Oncogene. 2002;21(43):6694–702. doi:10.1038/sj.onc.1205890.
Sonoda I, Imoto I, Inoue J, Shibata T, Shimada Y, Chin K, et al. Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma. Cancer Res. 2004;64(11):3741–7. doi:10.1158/0008-5472.can-04-0172.
Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69. doi:10.1038/nrc1840.
Song H, Bu G. MicroRNA-205 inhibits tumor cell migration through down-regulating the expression of the LDL receptor-related protein 1. Biochem Biophys Res Commun. 2009;388(2):400–5. doi:10.1016/j.bbrc.2009.08.020.
Kajihara I, Jinnin M, Harada M, Makino K, Honda N, Makino T, et al. miR-205 down-regulation promotes proliferation of dermatofibrosarcoma protuberans tumor cells by regulating LRP-1 and ERK phosphorylation. Arch Dermatol Res. 2014;306(4):367–74. doi:10.1007/s00403-014-1452-z.
Yang J, Annala M, Ji P, Wang G, Zheng H, Codgell D, et al. Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma. J Hematol Oncol. 2014;7(1):76. doi:10.1186/s13045-014-0076-2.
Yang JL. Investigation of osteosarcoma genomics and its impact on targeted therapy: an international collaboration to conquer human osteosarcoma. Chin J Cancer. 2014;33(12):575–80. doi:10.5732/cjc.014.10209.