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浙江大学学报(医学版)  2019, Vol. 48 Issue (3): 318-325    DOI: 10.3785/j.issn.1008-9292.2019.06.13
综述     
肿瘤细胞膜/质蛋白转位入核研究进展
朱紫菱(),谈静,邓红*()
浙江大学医学院病理与病理生理学系 浙江省蛋白质组学重点实验室, 浙江 杭州 310058
Nucleus translocation of membrane/cytoplasm proteins in tumor cells
ZHU Ziling(),TAN Jing,DENG Hong*()
Zhejiang Key Laboratory for Disease Proteomics, Department of Pathology, Zhejiang University School of Medicine, Hangzhou 310058, China
 全文: PDF(912 KB)   HTML( 17 )
摘要:

蛋白质作为生命物质的基础,在不同组织细胞中呈现不同的定位,执行不同的功能。同种蛋白质在不同的亚细胞区域定位可以发挥不同的功能,甚至表现出截然相反的作用。功能蛋白和结构蛋白都能够发生定位的改变,直接或间接参与信号转导。细胞癌变后,信号异常转导,原本在正常细胞的细胞膜/细胞质中表达的蛋白,却在肿瘤细胞中转位到细胞核而发生功能改变。结构蛋白入核主要通过蛋白断裂、蛋白含量改变以及蛋白相互结合实现。对关键蛋白分子的转位研究,有助于在临床应用中发现新的诊断标志物和治疗靶点。

关键词: 肿瘤/病理生理学蛋白质类/代谢信号传导肿瘤细胞综述    
Abstract:

Proteins are the physical basis of life and perform all kinds of life activities. Proteins have different orientations and function in different tissues. The same protein, located in different subcellular regions, can perform different and even opposite functions. Both functional and structural proteins are capable of undergoing re-localization which can directly or indirectly participate in signal transduction. Due to abnormal transduction of signals during carcinogenesis, the proteins originally expressed in the cytoplasm are translocated into the nucleus and lead to functional changes in the tumor tissue. The changes of protein localization are affected by many factors, including the interaction between proteins, expression level of proteins and the cleaved intracellular domain of transmembrane protein.

Key words: Neoplasms/physiopathology    Proteins/metabolism    Signal transduction    Tumor cells    Review
收稿日期: 2018-12-03 出版日期: 2019-09-04
CLC:  R730.2  
基金资助: 浙江省自然科学基金(LY12H16027, LY17H160017);国家自然科学基金(30870971)
通讯作者: 邓红     E-mail: ziling_zhu@126.com;hongdeng@zju.edu.cn
作者简介: 朱紫菱(1993-), 女, 硕士, 主要从事肿瘤分子病理学研究; E-mail: ziling_zhu@126.com; https://orcid.org/0000-0002-3847-3562
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引用本文:

朱紫菱, 谈静, 邓红. 肿瘤细胞膜/质蛋白转位入核研究进展[J]. 浙江大学学报(医学版), 2019, 48(3): 318-325.

ZHU Ziling, TAN Jing, DENG Hong. Nucleus translocation of membrane/cytoplasm proteins in tumor cells. J Zhejiang Univ (Med Sci), 2019, 48(3): 318-325.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.06.13        http://www.zjujournals.com/med/CN/Y2019/V48/I3/318

1 FERLAY J , COLOMBET M , SOERJOMATARAM I et al. Estimating the global cancer incidence and mortality in 2018:GLOBOCAN sources and methods[J]. Int J Cancer, 2019, 144 (8): 1941- 1953
2 GODBOLE A , LYGA S , LOHSE M J et al. Internalized TSH receptors en route to the TGN induce local Gs-protein signaling and gene transcription[J]. Nat Commun, 2017, 8 (1): 443
doi: 10.1038/s41467-017-00357-2
3 FRESIA C , VIGLIAROLO T , GUIDA L et al. G-protein coupling and nuclear translocation of the human abscisic acid receptor LANCL2[J]. Sci Rep, 2016, 6:26658
doi: 10.1038/srep26658
4 LU P, HONTECILLAS R, HORNE W T, et al. Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2[J/OL]. PLoS One, 2012, 7(4): e34643.
5 DURSUN E, GEZEN-AK D. Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin[J/OL]. PLoS One, 2017, 12(11): e0188605.
6 FOLLIS A V , LLAMBI F , MERRITT P et al. Pin1-induced proline isomerization in cytosolic p53 mediates BAX activation and apoptosis[J]. Mol Cell, 2015, 59 (4): 677- 684
doi: 10.1016/j.molcel.2015.06.029
7 LEVINE A J , OREN M . The first 30 years of p53:growing ever more complex[J]. Nat Rev Cancer, 2009, 9 (10): 749- 758
doi: 10.1038/nrc2723
8 DUFFY M J , SYNNOTT N C , MCGOWANP M et al. p53 as a target for the treatment of cancer[J]. Cancer Treat Rev, 2014, 40 (10): 1153- 1160
doi: 10.1016/j.ctrv.2014.10.004
9 ZHANG M Y , HARHAJ E W , BELL L et al. Bcl-3 expression and nuclear translocation are induced by granulocyte-macrophage colony-stimulating factor and erythropoietin in proliferating human erythroid precursors[J]. Blood, 1998, 92 (4): 1225- 1234
10 MASSOUMI R , CHMIELARSKA K , HENNECKE K et al. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling[J]. Cell, 2006, 125 (4): 665- 677
doi: 10.1016/j.cell.2006.03.041
11 WANG V Y , LI Y , KIM D et al. Bcl3 phosphorylation by Akt, Erk2, and IKK is required for its transcriptional activity[J]. Mol Cell, 2017, 67 (3): 484- 497.e5
doi: 10.1016/j.molcel.2017.06.011
12 SONG L , W?RMANN S , AI J et al. BCL3 reduces the sterile inflammatory response in pancreatic and biliary tissues[J]. Gastroenterology, 2016, 150 (2): 499- 512.e20
doi: 10.1053/j.gastro.2015.10.017
13 BRASIER A R , LU M , HAI T et al. NF-kappa B-inducible BCL-3 expression is an autoregulatory loop controlling nuclear p50/NF-kappa B1 residence[J]. J Biol Chem, 2001, 276 (34): 32080- 32093
doi: 10.1074/jbc.M102949200
14 CANEL M , BYRON A , SIMS A H et al. Nuclear FAK and Runx1 cooperate to regulate IGFBP3, cell-cycle progression, and tumor growth[J]. Cancer Res, 2017, 77 (19): 5301- 5312
doi: 10.1158/0008-5472.CAN-17-0418
15 WAN Q , TRUONGVO T , STEELE H E et al. Subcellular domain-dependent molecular hierarchy of SFK and FAK in mechanotransduction and cytokine signaling[J]. Sci Rep, 2017, 7 (1): 9033
doi: 10.1038/s41598-017-09495-5
16 LONG W , YI P , AMAZIT L et al. SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration[J]. Mol Cell, 2010, 37 (3): 321- 332
doi: 10.1016/j.molcel.2010.01.004
17 IZDEBSKA M , ZIELIN'SKA W , GRZANKA D et al. The role of actin dynamics and actin-binding proteins expression in epithelial-to-mesenchymal transition and its association with cancer progression and evaluation of possible therapeutic targets[J]. Biomed Res Int, 2018, 2018:4578373
18 CARIDI C P , D'AGOSTINO C , RYU T et al. Nuclear F-actin and myosins drive relocalization of heterochromatic breaks[J]. Nature, 2018, 559 (7712): 54- 60
doi: 10.1038/s41586-018-0242-8
19 GLOERICH M , BIANCHINI J M , SIEMERS K A et al. Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex[J]. Nat Commun, 2017, 8:13996
doi: 10.1038/ncomms13996
20 DU W , LIU X , FAN G et al. From cell membrane to the nucleus:an emerging role of E-cadherin in gene transcriptional regulation[J]. J Cell Mol Med, 2014, 18 (9): 1712- 1719
doi: 10.1111/jcmm.12340
21 CéSPEDES M V , LARRIBA M J , PAVóNM A et al. Site-dependent E-cadherin cleavage and nuclear translocation in a metastatic colorectal cancer model[J]. Am J Pathol, 2010, 177 (4): 2067- 2079
doi: 10.2353/ajpath.2010.100079
22 ELSTON M S , GILL A J , CONAGLENJ V et al. Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas[J]. J Clin Endocrinol Metab, 2009, 94 (4): 1436- 1442
doi: 10.1210/jc.2008-2075
23 OHISHI Y , ODA Y , KURIHARA S et al. Nuclear localization of E-cadherin but not beta-catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma[J]. Histopathology, 2011, 58 (3): 423- 432
doi: 10.1111/j.1365-2559.2011.03761.x
24 ZHAO Y , YU T , ZHANG N et al. Nuclear E-cadherin acetylation promotes colorectal tumorigenesis via enhancing beta-catenin activity[J]. Mol Cancer Res, 2019, 17 (2): 655- 665
doi: 10.1158/1541-7786.MCR-18-0637
25 FERBER E C , KAJITA M , WADLOW A et al. A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus[J]. J Biol Chem, 2008, 283 (19): 12691- 12700
doi: 10.1074/jbc.M708887200
26 YANCEY S B , JOHN S A , LAL R et al. The 43-kD polypeptide of heart gap junctions:immunolocalization, topology, and functional domains[J]. J Cell Biol, 1989, 108 (6): 2241- 2254
doi: 10.1083/jcb.108.6.2241
27 SIRNES S , LIND G E , BRUUN J et al. Connexins in colorectal cancer pathogenesis[J]. Int J Cancer, 2015, 137 (1): 1- 11
doi: 10.1002/ijc.28911
28 MOORER M C , HEBERT C , TOMLINSONR E et al. Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation[J]. J Cell Sci, 2017, 130 (3): 531- 540
doi: 10.1242/jcs.197285
29 DANG X , DOBLE B W , KARDAMI E . The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth[J]. Mol Cell Biochem, 2003, 242 (1-2): 35- 38
30 LAITMAN B M, ASP L, MARIANI J N, et al. The transcriptional activator Krüppel-like factor-6 is required for CNS myelination[J/OL]. PLoS Biol, 2016, 14(5): e1002467.
31 RODRíGUEZ E, ABURJANIA N, PRIEDIGKEITN M, et al. Nucleo-cytoplasmic localization domains regulate Krüppel-like factor 6(KLF6) protein stability and tumor suppressor function[J/OL]. PLoS One, 2010, 5(9). pii: e12639.
32 ZHANG Y , LEI C Q , HU Y H et al. Kruppel-like factor 6 is a co-activator of NF-kappaB that mediates p65-dependent transcription of selected downstream genes[J]. J Biol Chem, 2014, 289 (18): 12876- 12885
doi: 10.1074/jbc.M113.535831
33 SHOVAL I , LUDWIG A , KALCHEIM C . Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination[J]. Development, 2007, 134 (3): 491- 501
34 HAMBSCH B , GRINEVICH V , SEEBURGP H et al. γ-Protocadherins, presenilin-mediated release of C-terminal fragment promotes locus expression[J]. J Biol Chem, 2005, 280 (16): 15888- 15897
doi: 10.1074/jbc.M414359200
35 BERS D M . Membrane receptor neighborhoods:snuggling up to the nucleus[J]. Circ Res, 2013, 112 (2): 224- 226
doi: 10.1161/CIRCRESAHA.112.300494
36 MALIK Z A , STEIN I S , NAVEDOM F et al. Mission CaMKⅡgamma:shuttle calmodulin from membrane to nucleus[J]. Cell, 2014, 159 (2): 235- 237
doi: 10.1016/j.cell.2014.09.023
37 BARSHISHAT M , POLAK-CHARCON S , SCHWARTZ B . Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells[J]. Br J Cancer, 2000, 82 (1): 195- 203
doi: 10.1054/bjoc.1999.0899
38 LECUIT T , YAP A S . E-cadherin junctions as active mechanical integrators in tissue dynamics[J]. Nat Cell Biol, 2015, 17 (5): 533- 539
doi: 10.1038/ncb3136
39 LABERNADIE A , KATO T , BRUGUéS A et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion[J]. Nat Cell Biol, 2017, 19 (3): 224- 237
doi: 10.1038/ncb3478
40 MCCREA P D , GOTTARDI C J . Beyond beta-catenin:prospects for a larger catenin network in the nucleus[J]. Nat Rev Mol Cell Biol, 2016, 17 (1): 55- 64
41 CLEVERS H , NUSSE R . Wnt/beta-catenin signaling and disease[J]. Cell, 2012, 149 (6): 1192- 1205
doi: 10.1016/j.cell.2012.05.012
42 DEBRUINE Z J , XU H E , MELCHER K . Assembly and architecture of the Wnt/beta-catenin signalosome at the membrane[J]. Br J Pharmacol, 2017, 174 (24): 4564- 4574
doi: 10.1111/bph.14048
43 DIAMANTOPOULOU Z , WHITE G , MZH F et al. TIAM1 antagonizes TAZ/YAP both in the destruction complex in the cytoplasm and in the nucleus to inhibit invasion of intestinal epithelial cells[J]. Cancer Cell, 2017, 31 (5): 621- 634
doi: 10.1016/j.ccell.2017.03.007
44 AYLON Y , OFIR-ROSENFELD Y , YABUTA N et al. The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1[J]. Genes Dev, 2010, 24 (21): 2420- 2429
doi: 10.1101/gad.1954410
45 VIGNERON A M , LUDWIG R L , VOUSDENK H . Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP[J]. Genes Dev, 2010, 24 (21): 2430- 2439
doi: 10.1101/gad.1954310
46 GUO L , TENG L . YAP/TAZ for cancer therapy:opportunities and challenges (review)[J]. Int J Oncol, 2015, 46 (4): 1444- 1452
doi: 10.3892/ijo.2015.2877
47 LEE K W , COBB L J , PAHARKOVA-VATCHKOVA V et al. Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3[J]. Carcinogenesis, 2007, 28 (8): 1653- 1658
doi: 10.1093/carcin/bgm088
48 CAO Z , KOOCHEKPOUR S , STRUP S E et al. Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells[J]. Oncotarget, 2017, 8 (45): 78507- 78519
49 SANTUCCI M , VIGNUDELLI T , FERRARI S et al. The hippo pathway and YAP/TAZ-TEAD protein-protein interaction as targets for regenerative medicine and cancer treatment[J]. J Med Chem, 2015, 58 (12): 4857- 4873
doi: 10.1021/jm501615v
50 SMITH J M , HEDMAN A C , SACKS D B . IQGAPs choreograph cellular signaling from the membrane to the nucleus[J]. Trends Cell Biol, 2015, 25 (3): 171- 184
doi: 10.1016/j.tcb.2014.12.005
51 CHAN S W , LIM C J , GUO K et al. A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells[J]. Cancer Res, 2008, 68 (8): 2592- 2598
doi: 10.1158/0008-5472.CAN-07-2696
52 VITALE M L, GARCIA C J, AKPOVI C D, et al. Distinctive actions of connexin 46 and connexin 50 in anterior pituitary folliculostellate cells[J/OL]. PLoS One, 2017, 12(7): e0182495.
53 MOORBY C , PATEL M . Dual functions for connexins:Cx43 regulates growth independently of gap junction formation[J]. Exp Cell Res, 2001, 271 (2): 238- 248
doi: 10.1006/excr.2001.5357
54 HAO F, XU Q, WANG J, et al. Lipophilic statins inhibit YAP nuclear localization, co-activator activity and colony formation in pancreatic cancer cells and prevent the initial stages of pancreatic ductal adenocarcinoma in KrasG12D mice[J/OL]. PLoS One, 2019, 14(5): e0216603.
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