国际口腔医学杂志 ›› 2017, Vol. 44 ›› Issue (5): 614-618.doi: 10.7518/gjkq.2017.05.024

• 综述 • 上一篇    

Hippo/YAP信号通路与细胞增殖相关信号通路交叉作用的研究进展

王琪, 陈希彦, 文勇   

  1. 山东大学口腔医院种植科,山东省口腔组织再生重点实验室 济南 250012
  • 收稿日期:2016-11-28 修回日期:2017-03-07 出版日期:2017-09-01 发布日期:2017-09-01
  • 通讯作者: 文勇,副教授,博士,Email:593494509@qq.com
  • 作者简介:王琪,硕士,Email:1574304182@qq.com
  • 基金资助:
    国家自然科学基金(81300885); 山东省重点研发计划(2016GSF201115,2016GSF201220); 山东大学青年学者未来计划(2015WLJH53)

Research progress on the crosstalk between Hippo/YAP signaling pathway and cell proliferation-related signaling pathways

Wang Qi, Chen Xiyan, Wen Yong.   

  1. Dept. of Implantology, Hospital of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan 250012, China
  • Received:2016-11-28 Revised:2017-03-07 Online:2017-09-01 Published:2017-09-01
  • Supported by:
    ; This study was supported by National Natural Science Foundation of China(81300885), Shandong Provincial key research and development program(2016GSF201115, 2016GSF201220) and Young Scholars Program of Shandong University (2015WLJH53).

摘要: Hippo/YAP信号通路首次被发现于果蝇中,在哺乳动物中具有高度保守的特性,可通过直接或间接地调节细胞增殖、程序性细胞死亡以起到平衡机体内环境稳态、维持器官大小的作用。YAP作为Hippo信号通路中的一个转录共激活因子,与磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、Wnt/β-联蛋白、细胞外信号调节激酶(ERK)1/2等通路中相关分子相互作用,使得Hippo通路与其他增殖调控相关信号通路形成“交通”,构成一个复杂的信号通路网,共同调控细胞的增殖。本文就目前对Hippo信号通路中共激活因子YAP与增殖调控信号通路间的交叉影响及其机制的研究进展作一综述。

关键词: Hippo/YAP信号通路, 磷脂酰肌醇3-激酶/蛋白激酶B, Wnt/β, -联蛋白, 细胞外信号调节激酶, 增殖

Abstract: Hippo/YAP signaling pathway was discovered in Drosophila firstly. It is highly conserved in mammals and can regulate cell proliferation and apoptosis directly or indirectly, which can keep the homeostasis and size of organs in vivo. YAP can act as a transcription coactivator in Hippo signaling pathway with some moleculars in phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT), Wnt/β-catenin and extracellular signal-regulated kinases(ERK) 1/2. Hippo pathway is involved in the complex signaling pathway net, as a crosstalk between Hippo and other proliferation-related signaling pathways exists, which regulates cell proliferation. In this study, we summarize the research progress of the effect and mechanism of this crosstalk between coactivator YAP in Hippo signaling pathway and signaling pathways-controlled proliferation.

Key words: Hippo/YAP signaling pathway, phosphatidylinositol 3-kinase/protein kinase B, Wnt/β, -catenin, extracellular signal regulated kinase, proliferation

中图分类号: 

  • Q786
[1] Mo JS, Park HW, Guan KL. The Hippo signaling pathway in stem cell biology and cancer[J]. EMBO Rep, 2014, 15(6):642-656.
[2] Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer[J]. Cell, 2015, 163(4):811-828.
[3] Johnson R, Halder G. The two faces of Hippo: tar-geting the Hippo pathway for regenerative medicine and cancer treatment[J]. Nat Rev Drug Discov, 2014, 13(1):63-79.
[4] Heinemann A, Cullinane C, De Paoli-Iseppi R, et al. Combining BET and HDAC inhibitors synergisti-cally induces apoptosis of melanoma and suppresses AKT and YAP signaling[J]. Oncotarget, 2015, 6(25): 21507-21521.
[5] Lin Z, Zhou P, von Gise A, et al. Pi3kcb links Hippo-YAP and PI3K-AKT signaling pathways to promote cardiomyocyte proliferation and survival[J]. Circ Res, 2015, 116(1):35-45.
[6] Straßburger K, Tiebe M, Pinna F, et al. Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP[J]. Dev Biol, 2012, 367(2):187-196.
[7] Li XJ, Leem SH, Park MH, et al. Regulation of YAP through an Akt-dependent process by 3,3’-diindolyl-methane in human colon cancer cells[J]. Int J Oncol, 2013, 43(6):1992-1998.
[8] You B, Yang YL, Xu Z, et al. Inhibition of ERK1/2 down-regulates the Hippo/YAP signaling pathway in human NSCLC cells[J]. Oncotarget, 2015, 6(6): 4357-4368.
[9] Yu S, Cai X, Wu C, et al. Adhesion glycoprotein CD44 functions as an upstream regulator of a net-work connecting ERK, AKT and Hippo-YAP path-ways in cancer progression[J]. Oncotarget, 2015, 6 (5):2951-2965.
[10] Suzuki A, Pelikan RC, Iwata J. WNT/β-catenin signaling regulates multiple steps of myogenesis by regulating step-specific targets[J]. Mol Cell Biol, 2015, 35(10):1763-1776.
[11] Saito-Diaz K, Chen TW, Wang X, et al. The way Wnt works: components and mechanism[J]. Growth Factors, 2013, 31(1):1-31.
[12] Barry ER, Morikawa T, Butler BL, et al. Restriction of intestinal stem cell expansion and the regenerative response by YAP[J]. Nature, 2013, 493(7430):106- 110.
[13] Heallen T, Zhang M, Wang J, et al. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size[J]. Science, 2011, 332 (6028):458-461.
[14] Rosenbluh J, Nijhawan D, Cox AG, et al. β-Catenin-driven cancers require a YAP1 transcriptional com-plex for survival and tumorigenesis[J]. Cell, 2012, 151(7):1457-1473.
[15] Varelas X, Wrana JL. Coordinating developmental signaling: novel roles for the Hippo pathway[J]. Trends Cell Biol, 2012, 22(2):88-96.
[16] Hatzis P, van der Flier LG, van Driel MA, et al. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells[J]. Mol Cell Biol, 2008, 28(8):2732-2744.
[17] Konsavage WM Jr, Kyler SL, Rennoll SA, et al. Wnt/β-catenin signaling regulates Yes-associated protein(YAP) gene expression in colorectal carcinoma cells[J]. J Biol Chem, 2012, 287(15):11730-11739.
[18] Barry ER, Morikawa T, Butler BL, et al. Restriction of intestinal stem cell expansion and the regenerative response by YAP[J]. Nature, 2013, 493(7430):106- 110.
[19] Wang J, Park JS, Wei Y, et al. TRIB2 acts down-stream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPα function[J]. Mol Cell, 2013, 51 (2):211-225.
[20] Hussey GS, Chaudhury A, Dawson AE, et al. Identi-fication of an mRNP complex regulating tumori-genesis at the translational elongation step[J]. Mol Cell, 2011, 41(4):419-431.
[21] Xie Q, Chen J, Feng H, et al. YAP/TEAD-mediated transcription controls cellular senescence[J]. Cancer Res, 2013, 73(12):3615-3624.
[22] Varelas X, Sakuma R, Samavarchi-Tehrani P, et al. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal [J]. Nat Cell Biol, 2008, 10(7):837-848.
[23] Fujii M, Toyoda T, Nakanishi H, et al. TGF-β syner-gizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth[J]. J Exp Med, 2012, 209(3):479-494.
[24] Xia Y, Chang T, Wang Y, et al. YAP promotes ovarian cancer cell tumorigenesis and is indicative of a poor prognosis for ovarian cancer patients[J]. PLoS One, 2014, 9(3):e91770.
[25] Shi Y, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus[J]. Cell, 2003, 113(6):685-700.
[26] Tsukazaki T, Chiang TA, Davison AF, et al. SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor[J]. Cell, 1998, 95(6):779-791.
[27] Dobolyi A, Vincze C, Pál G, et al. The neuroprotec-tive functions of transforming growth factor beta proteins[J]. Int J Mol Sci, 2012, 13(7): 8219-8258.
[28] Hayashi H, Abdollah S, Qiu Y, et al. The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling[J]. Cell, 1997, 89(7):1165-1173.
[29] Ferrigno O, Lallemand F, Verrecchia F, et al. Yes-associated protein(YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-β/Smad signaling[J]. Oncogene, 2002, 21(32):4879-4884.
[30] Piersma B, Bank RA, Boersema M. Signaling in fib-rosis: TGF-β, WNT, and YAP/TAZ converge[J]. Front Med(Lausanne), 2015, 2:59.
[1] 杨宇轩,张海霞,王爽. 釉原蛋白在牙周组织再生中的生物学作用[J]. 国际口腔医学杂志, 2019, 46(2): 191-196.
[2] 李媛媛,程斌,王韵. 长链非编码RNA lnc-p26090对口腔鳞状细胞癌细胞糖酵解及增殖的影响[J]. 国际口腔医学杂志, 2018, 45(6): 628-634.
[3] 王志强,刘娅丽,马丽娟,杨兰,王若宇,高舒婷. 红景天苷对人舌鳞状细胞癌CAL-27细胞增殖、凋亡、周期及迁移的影响[J]. 国际口腔医学杂志, 2018, 45(6): 678-685.
[4] 詹烨明, 张明珠. 药物性牙龈增生与细胞增殖和凋亡相关性的研究进展[J]. 国际口腔医学杂志, 2018, 45(2): 199-203.
[5] 班华杰1 王代友2. 细胞外信号调节激酶信号转导通路在牙发生和再生中的作用[J]. 国际口腔医学杂志, 2015, 42(6): 694-698.
[6] 程群,杨明华,陈斌,刘娟,闫福华. Er:YAG激光对人牙周膜细胞增殖和迁移的影响[J]. 国际口腔医学杂志, 2015, 42(2): 135-139.
[7] 何鲲1 程祥荣2 张曦木3. 釉基质蛋白对人牙囊和牙周膜细胞黏附增殖的影响[J]. 国际口腔医学杂志, 2014, 41(5): 536-540.
[8] 王红梅 乔树芳. 增殖性化脓性口炎[J]. 国际口腔医学杂志, 2013, 40(6): 826-828.
[9] 吉秋霞 袁昌青 宋文斌 武宏. 壳聚糖季铵盐对人牙周膜成纤维细胞增殖及细胞周期影响的实验研究[J]. 国际口腔医学杂志, 2013, 40(5): 588-591.
[10] 张舒 王璟综述 林云锋审校. 材料表面的微图形对细胞行为的影响[J]. 国际口腔医学杂志, 2013, 40(4): 544-546.
[11] 肖惟雄 班兆阳综述 朱智敏审校. 低强度脉冲超声在骨治疗中的生物学机制[J]. 国际口腔医学杂志, 2013, 40(4): 557-560.
[12] 王晓婧 朱卓立 于海洋. 微振动对血管内皮细胞增殖和分化的影响[J]. 国际口腔医学杂志, 2013, 40(3): 288-290.
[13] 龚启梅综述 凌均棨审校. 低氧对成体干细胞增殖和分化的影响[J]. 国际口腔医学杂志, 2011, 38(6): 696-699.
[14] 邵扬1 张广耘2 袁晓2. 周期性张应力对牙周膜成纤维细胞增殖的影响[J]. 国际口腔医学杂志, 2011, 38(4): 384-387.
[15] 戴丽娜 苏勤 周陈晨 王辉 陈娇 张平. 银杏酚酸提高Tca8113 对化学治疗药物敏感性的研究[J]. 国际口腔医学杂志, 2011, 38(3): 268-273.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 张京剧. 青年期至中年期颅面复合体变化的头影测量研究[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 高卫民,李幸红. 发达国家牙医学院口腔种植学教学现状[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 汪月月,郭莉莉. 口腔机能与老化—痴呆危险因素流行病学研究[J]. 国际口腔医学杂志, 1999, 26(04): .
[5] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[6] 杨儒壮 孙宏晨 欧阳喈. 纳米级高分子支架材料在组织工程中的研究进展[J]. 国际口腔医学杂志, 2004, 31(02): 126 -128 .
[7] . 第4届中日口腔医学大会征稿通知[J]. 国际口腔医学杂志, 2008, 35(S1): .
[8] 聂盼 李婧 李伟. Activator 治疗骨性Ⅱ类畸形的临床应用[J]. 国际口腔医学杂志, 2011, 38(4): 380 -383 .
[9] 李佳岭1 李小兵2 李佳园3. 内收下切牙对下切牙区牙槽骨改建的影响[J]. 国际口腔医学杂志, 2011, 38(4): 392 -394 .
[10] 陈哲1 王璟2综述 王虎3审校. 音乐疗法在口腔领域中的应用[J]. 国际口腔医学杂志, 2011, 38(6): 734 -737 .