Hippo信号通路与肝脏稳态调控及疾病发生

doi:10.16288/j.yczz.17-064

遗传 ›› 2017, Vol. 39 ›› Issue (7): 607-616.doi: 10.16288/j.yczz.17-064

Hippo信号通路与肝脏稳态调控及疾病发生

李玉席(),李俊宏,周大旺()

厦门大学生命科学学院,细胞信号网络协同创新中心,厦门 361102

收稿日期:2017-02-26 修回日期:2017-05-05 出版日期:2017-07-20 发布日期:2017-05-31
作者简介:李玉席,博士研究生,研究方向：细胞生物学。E-mail: liyuxi0608@foxmail.com|周大旺,教授,博士生导师,研究方向：细胞生物学。E-mail: dwzhou@xmu.edu.cn
基金资助:
国家自然科学基金项目(31625010,U1505224,J1310027)

Hippo signaling pathway in liver tissue homeostasis

Li Yuxi(),Li Junhong,Zhou Dawang(),

Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China

Received:2017-02-26 Revised:2017-05-05 Online:2017-07-20 Published:2017-05-31
Supported by:
the National Natural Science Foundation of China(31625010,U1505224,J1310027)

摘要/Abstract

摘要：

肝脏是人体最重要的器官之一,乙肝等病毒性与酒精等非病毒性因素诱发的肝损伤引起肝脏功能衰竭、再生重塑障碍、肝癌等疾病是我国重大社会健康问题,因此,研究肝脏稳态的调控机制对肝病的预防和临床治疗至关重要。Hippo信号通路参与了哺乳动物多种细胞和器官的稳态调控。最近研究表明,Hippo信号通路在肝脏发育、肝细胞命运决定、肝脏再生和癌症发生发展等过程中都发挥了非常重要的作用。因此,Hippo信号通路可成为肝脏相关疾病的治疗提供了新的靶点。本文综述了Hippo信号通路与肝脏稳态调控的相关研究及最新进展,以期为研究肝脏发育和肝脏相关疾病的治疗提供新的思路和策略。

关键词: Hippo/Yap, 肝脏发育, 肝癌, 肝再生

Abstract:

Liver cancer and diseases have become the leading cause of deaths in China. Liver diseases including liver failure and liver cancer can be genetic or caused by a variety of factors that damage the liver, such as viruses and alcohol overdose. However, the underlying mechanisms that maintain liver homeostasis remain unclear. Recent studies show that the Hippo signaling pathway plays a critical role in maintaining liver tissue homeostasis. Dysregulation of the Hippo signaling pathway impairs liver regeneration and remarkly enhances liver overgrowth and tumorigenesis. In this review, we summarize recent progresses on the roles and regulation mechanisms of the Hippo signaling pathway in liver development and diseases.

Key words: Hippo/Yap, liver development, liver cancer, liver regeneration

李玉席, 李俊宏, 周大旺. Hippo信号通路与肝脏稳态调控及疾病发生[J]. 遗传, 2017, 39(7): 607-616.

Li Yuxi, Li Junhong, Zhou Dawang, . Hippo signaling pathway in liver tissue homeostasis[J]. Hereditas(Beijing), 2017, 39(7): 607-616.

参考文献

[1]	Zhou DW, Zhang YY, Wu HT, Barry E, Yin Y, Lawrence E, Dawson D, Willis JE, Markowitz SD, Camargo FD, Avruch J. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci USA, 2011, 108(49): E1312-E1320.
[2]	Zhou Q, Li L, Zhao B, Guan KL. The hippo pathway in heart development, regeneration, and diseases. Circ Res, 2015, 116(8): 1431-1447.
[3]	Zhou DW, Medoff BD, Chen LF, Li LQ, Zhang XF, Praskova M, Liu M, Landry A, Blumberg RS, Boussiotis VA, Xavier R, Avruch J. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of na?ve T cells. Proc Natl Acad Sci USA, 2008, 105(51): 20321-20326.
[4]	Geng J, Sun XF, Wang P, Zhang SH, Wang XZ, Wu HT, Hong LX, Xie CC, Li X, Zhao H, Liu QX, Jiang MT, Chen QH, Zhang JJ, Li Y, Song SY, Wang HR, Zhou RB, Johnson RL, Chien KY, Lin SC, Han JH, Avruch J, Chen LF, Zhou DW. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nat Immunol, 2015, 16(11): 1142-1152.
[5]	Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev, 2013, 27(4): 355-371.
[6]	Huang JB, Wu SA, Barrera J, Matthews K, Pan DJ. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell, 2005, 122(3): 421-434.
[7]	Wu SA, Huang JB, Dong JC, Pan DJ. hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell, 2003, 114(4): 445-456.
[8]	Chan EHY, Nousiainen M, Chalamalasetty RB, Sch?fer A, Nigg EA, Silljé HHW. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene, 2005, 24(12): 2076-2086.
[9]	Yin F, Yu JZ, Zheng YG, Chen Q, Zhang NL, Pan DJ. Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell, 2013, 154(6): 1342-1355.
[10]	Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H, Halder G. The tumour- suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol, 2006, 8(1): 27-36.
[11]	Bennett FC, Harvey KF. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr Biol, 2006, 16(21): 2101-2110.
[12]	Greenbaum LE. The ductal plate: a source of progenitors and hepatocytes in the adult liver. Gastroenterology, 2011, 141(4): 1152-1155.
[13]	Zhang NL, Bai HB, David KK, Dong JX, Zheng YG, Cai J, Giovannini M, Liu PT, Anders RA, Pan DJ. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell, 2010, 19(1): 27-38.
[14]	Fitamant J, Kottakis F, Benhamouche S, Tian HS, Chuvin N, Parachoniak CA, Nagle JM, Perera RM, Lapouge M, Deshpande V, Zhu AX, Lai A, Min B, Hoshida Y, Avruch J, Sia D, Campreciós G, McClatchey AI, Llovet JM, Morrissey D, Raj L, Bardeesy N. YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression. Cell Rep, 2015, 10(10): 1692-1707.
[15]	Alder O, Cullum R, Lee S, Kan AC, Wei W, Yi YY, Garside VC, Bilenky M, Griffith M, Morrissy AS, Robertson GA, Thiessen N, Zhao YJ, Chen Q, Pan DJ, Jones SJM, Marra MA, Hoodless PA. Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell Rep, 2014, 9(1): 261-271.
[16]	Yimlamai D, Christodoulou C, Galli GG, Yanger K, Pepe-Mooney B, Gurung B, Shrestha K, Cahan P, Stanger BZ, Camargo FD. Hippo pathway activity influences liver cell fate. Cell, 2014, 157(6): 1324-1338.
[17]	Hofmann JJ, Zovein AC, Koh H, Radtke F, Weinmaster G, Iruela-Arispe ML. Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development, 2010, 137(23): 4061-4072.
[18]	Lee DH, Park JO, Kim TS, Kim SK, Kim TH, Kim MC, Park GS, Kim JH, Kuninaka S, Olson EN, Saya H, Kim SY, Lee H, Lim DS. LATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development. Nat Commun, 2016, 7: 11961.
[19]	Bai HB, Zhang NL, Xu Y, Chen Q, Khan M, Potter JJ, Nayar SK, Cornish T, Alpini G, Bronk S, Pan DJ, Anders RA. Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology, 2012, 56(3): 1097-1107.
[20]	Wu HT, Xiao YB, Zhang SH, Ji SY, Wei LY, Fan FQ, Geng J, Tian J, Sun XF, Qin FN, Jin CN, Lin JJ, Yin ZY, Zhang T, Luo LZ, Li Y, Song SY, Lin SC, Deng XM, Camargo F, Avruch J, Chen LF, Zhou DW. The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense. Cell Rep, 2013, 3(5): 1663-1677.
[21]	Zhou DW, Conrad C, Xia F, Park JS, Payer B, Yin Y, Lauwers GY, Thasler W, Lee JT, Avruch J, Bardeesy N. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell, 2009, 16(5): 425-438.
[22]	Dong JX, Feldmann G, Huang JB, Wu SA, Zhang NL, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan DJ. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell, 2007, 130(6): 1120-1133.
[23]	Harada N, Oshima H, Katoh M, Tamai Y, Oshima M, Taketo MM. Hepatocarcinogenesis in mice with β-catenin and Ha-ras gene mutations. Cancer Res, 2004, 64(1): 48-54.
[24]	Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, McClatchey AI. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev, 2010, 24(16): 1718-1730.
[25]	Song H, Mak KK, Topol L, Yun KS, Hu JX, Garrett L, Chen YB, Park O, Chang J, Simpson RM, Wang CY, Gao B, Jiang J, Yang YZ. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci USA, 2010, 107(4): 1431-1436.
[26]	Lu L, Li Y, Kim SM, Bossuyt W, Liu P, Qiu Q, Wang YD, Halder G, Finegold MJ, Lee JS, Johnson RL. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci USA, 2010, 107(4): 1437-1442.
[27]	Lee KP, Lee JH, Kim TS, Kim TH, Park HD, Byun JS, Kim MC, Jeong WI, Calvisi DF, Kim JM, Lim DS. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA, 2010, 107(18): 8248-8253.
[28]	Yi J, Lu L, Yanger K, Wang WQ, Sohn BH, Stanger BZ, Zhang M, Martin JF, Ajani JA, Chen JJ, Lee JS, Song SM, Johnson RL. Large tumor suppressor homologs 1 and 2 regulate mouse liver progenitor cell proliferation and maturation through antagonism of the coactivators YAP and TAZ. Hepatology, 2016, 64(5): 1757-1772.
[29]	Nishio M, Sugimachi K, Goto H, Wang J, Morikawa T, Miyachi Y, Takano Y, Hikasa H, Itoh T, Suzuki SO, Kurihara H, Aishima S, Leask A, Sasaki T, Nakano T, Nishina H, Nishikawa Y, Sekido Y, Nakao K, Shin-Ya K, Mimori K, Suzuki A. Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b- deficient mice. Proc Natl Acad Sci USA, 2016, 113(1): E71-E80.
[30]	Camargo FD, Gokhale S, Johnnidis JB, Fu DD, Bell GW, Jaenisch R, Brummelkamp TR. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol, 2007, 17(23): 2054-2060.
[31]	Lemaigre FP. Development of the biliary tract. Mech Dev, 2003, 120(1): 81-87.
[32]	Geisler F, Nagl F, Mazur PK, Lee M, Zimber-Strobl U, Strobl LJ, Radtke F, Schmid RM, Siveke JT. Liver-specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice. Hepatology, 2008, 48(2): 607-616.
[33]	Moroishi T, Park HW, Qin BD, Chen Q, Meng ZP, Plouffe SW, Taniguchi K, Yu FX, Karin M, Pan DJ, Guan KL. A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev, 2015, 29(12): 1271-1284.
[34]	Jungermann K, Katz N. Functional specialization of different hepatocyte populations. Physiol Rev, 1989, 69(3): 708-764.
[35]	Oh S, Lee D, Kim T, Kim TS, Oh HJ, Hwang CY, Kong YY, Kwon KS, Lim DS. Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse. Mol Cell Biol, 2009, 29(23): 6309-6320.
[36]	McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev, 1998, 12(8): 1121-1133.
[37]	Chen Q, Zhang NL, Xie R, Wang W, Cai J, Choi KS, David KK, Huang B, Yabuta N, Nojima H, Anders RA, Pan DJ. Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP. Genes Dev, 2015, 29(12): 1285-1297.
[38]	Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F, Chiba S, Mizuno K, Suzuki SO, Dong YY, Tokuda M, Morikawa T, Hikasa H, Eggenschwiler J, Yabuta N, Nojima H, Nakagawa K, Hata Y, Nishina H, Mimori K, Mori M, Sasaki T, Mak TW, Nakano T, Itami S, Suzuki A. Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice. J Clin Invest, 2012, 122(12): 4505-4518.
[39]	Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 2006, 6(9): 674-687.
[40]	Jie L, Fan W, Wei QD, Ying QZ, Ling X, Miao S, Ping C, Chuan YG. The hippo-yes association protein pathway in liver cancer. Gastroenterol Res Pract, 2013, ( 2013-8-6), 2013, 2013(3): 187070.
[41]	Zender L, Spector MS, Xue W, Flemming P, Cordon- Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, Mu D, Lucito R, Powers S, Lowe SW. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell, 2006, 125(7): 1253-1267.
[42]	Xu MZ, Yao TJ, Lee NPY, Ng IOL, Chan YT, Zender L, Lowe SW, Poon RTP, Luk JM. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer, 2009, 115(19): 4576-4585.
[43]	Tu KS, Yang W, Li C, Zheng X, Lu ZT, Guo C, Yao YM, Liu QG. Fbxw7 is an independent prognostic marker and induces apoptosis and growth arrest by regulating YAP abundance in hepatocellular carcinoma. Mol Cancer, 2014, 13: 110.
[44]	Mao B, Hu F, Cheng J, Wang P, Xu M, Yuan F, Meng S, Wang Y, Yuan Z, Bi W. SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in hepatocellular carcinoma. Oncogene, 2014, 33(11): 1468-1474.
[45]	Anakk S, Bhosale M, Schmidt VA, Johnson RL, Finegold MJ, Moore DD. Bile acids activate YAP to promote liver carcinogenesis. Cell Rep, 2013, 5(4): 1060-1069.
[46]	Zhao B, Wei XM, Li WQ, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu JD, Li L, Zheng P, Ye KQ, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev, 2007, 21(21): 2747-2761.
[47]	Overholtzer M, Zhang JM, Smolen GA, Muir B, Li WM, Sgroi DC, Deng CX, Brugge JS, Haber DA. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA, 2006, 103(33): 12405-12410.
[48]	Kim GJ, Kim H, Park YN. Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma. PLoS One, 2013, 8(9): e75449.
[49]	Leung CON, Mak WN, Kai AKL, Chan KS, Lee TKW, Ng IOL, Lo RCL. Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/ β-catenin signaling. Oncotarget, 2016, 7(20): 29371-29386.
[50]	Wang XB, Zheng Z, Caviglia JM, Corey KE, Herfel T, Cai BS, Masia R, Chung RT, Lefkowitch JH, Schwabe RF, Tabas I. Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab, 2016, 24(6): 848-862.
[51]	Zhang DY, Friedman SL. Fibrosis-dependent mechanisms of hepatocarcinogenesis. Hepatology, 2012, 56(2): 769-775.
[52]	Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, Anders RA, Liu JO, Pan DJ. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev, 2012, 26(12): 1300-1305.
[53]	Liu AM, Xu MZ, Chen JF, Poon RT, Luk JM. Targeting YAP and Hippo signaling pathway in liver cancer. Expert Opin Ther Targets, 2010, 14(8): 855-868.
[54]	Perra A, Kowalik MA, Ghiso E, Ledda-Columbano GM, Di Tommaso L, Angioni MM, Raschioni C, Testore E, Roncalli M, Giordano S, Columbano A. YAP activation is an early event and a potential therapeutic target in liver cancer development. J Hepatol, 2014, 61(5): 1088-1096.
[55]	Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology, 2006, 43(S1): S45-S53.
[56]	Michalopoulos GK. Liver regeneration after partial hepatectomy. Am J Pathol, 2010, 176(1): 2-13.
[57]	Udan RS, Kango-Singh M, Nolo R, Tao CY, Halder G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol, 2003, 5(10): 914-920.
[58]	Harvey KF, Pfleger CM, Hariharan IK. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell, 2003, 114(4): 457-467.
[59]	Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol, 2011, 13(8): 877-883.
[60]	Xin M, Kim Y, Sutherland LB, Murakami M, Qi XX, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, Richardson JA, Sadek HA, Bassel-Duby R, Olson EN. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA, 2013, 110(34): 13839-13844.
[61]	Karpowicz P, Perez J, Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development, 2010, 137(24): 4135-4145.
[62]	Grijalva JL, Huizenga M, Mueller K, Rodriguez S, Brazzo J, Camargo F, Sadri-Vakili G, Vakili K. Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration. Am J Physiol Gastrointest Liver Physiol, 2014, 307(2): G196-G204.
[63]	Fan FQ, He ZX, Kong LL, Chen QH, Yuan Q, Zhang SH, Ye JJ, Liu H, Sun XF, Geng J, Yuan LZ, Hong LX, Xiao C, Zhang WJ, Sun XH, Li YZ, Wang P, Huang LH, Wu XR, Ji ZL, Wu Q, Xia NS, Gray NS, Chen LF, Yun CH, Deng XM, Zhou DW. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Sci Transl Med, 2016, 8(352): 352ra108.
[64]	Loforese G, Malinka T, Keogh A, Baier F, Simillion C, Montani M, Halazonetis TD, Candinas D, Stroka D. Impaired liver regeneration in aged mice can be rescued by silencing Hippo core kinases MST1 and MST2. EMBO Mol Med, 2017, 9(1): 46-60.
[65]	Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, Hosokawa S, Elbahrawy A, Soeda T, Koizumi M, Masui T, Kawaguchi M, Takaori K, Doi R, Nishi E, Kakinoki R, Deng JM, Behringer RR, Nakamura T, Uemoto S. Continuous cell supply from a Sox9- expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet, 2011, 43(1): 34-41.
[66]	Zhao B, Ye X, Yu JD, Li L, Li WQ, Li SM, Yu JJ, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev, 2008, 22(14): 1962-1971.
[67]	Bai HB, Gayyed MF, Lam-Himlin DM, Klein AP, Nayar SK, Xu Y, Khan M, Argani P, Pan DJ, Anders RA. Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies. Hum Pathol, 2012, 43(9): 1376-1385.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

Hippo信号通路与肝脏稳态调控及疾病发生

Hippo signaling pathway in liver tissue homeostasis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 14

编辑推荐

Metrics

[1]	张玲, 何建波. GATA6在肝脏发育中的作用及调控机制[J]. 遗传, 2018, 40(1): 22-32.
[2]	王永煜,余薇,周斌. Hippo信号通路与心血管发育及疾病调控[J]. 遗传, 2017, 39(7): 576-587.
[3]	孙凌云, 李星逾, 孙志为. 原发性肝癌的表观遗传学及其治疗[J]. 遗传, 2015, 37(6): 517-527.
[4]	王棋文, 靳伟, 常翠芳, 徐存拴. 基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用[J]. 遗传, 2015, 37(3): 276-282.
[5]	王棋文,常翠芳,谷宁宁,潘翠云,徐存拴. 自噬在肝再生中的作用[J]. 遗传, 2015, 37(11): 1116-1124.
[6]	许飞, 张进, 马端. Hippo/YAP和Wnt/β-catenin通路的对话[J]. 遗传, 2014, 36(2): 95-102.
[7]	王泽，文园园，程振朝，郭学强，张新胜，徐存拴. 新基因BM390716、BI274487和AA963863与大鼠再生肝8种细胞的细胞外基质代谢[J]. 遗传, 2011, 33(4): 378-388.
[8]	常翠芳，王改平，朱秋实，王磊，张富春，马纪，徐存拴. 大鼠再生肝8种细胞的丝氨酸族氨基酸代谢相关基因的转录谱[J]. 遗传, 2010, 32(8): 829-838.
[9]	李红蕾，陈晓光，张富春，马纪，徐存拴. 细胞外基质相关基因在大鼠肝再生中表达模式分析[J]. 遗传, 2008, 30(3): 333-340.
[10]	黄学文，赵琪，陈道桢，张丽珊. 肝癌组织中线粒体DNA D-Loop区碱基变异与ROS水平[J]. 遗传, 2005, 27(1): 14-20.
[11]	林俊堂，李玉昌，张会勇，徐存拴. 常氏肝癌细胞cDNA文库的构建及ADAMs相关基因的免疫筛选与序列分析[J]. 遗传, 2004, 26(6): 793-796.
[12]	李玉昌，徐存拴，张云汉. 应用抑制性消减杂交技术克隆大鼠肝再生过程中特异表达基因[J]. 遗传, 2002, 24(2): 152-154.
[13]	王兆，应康，林盛榕，吴海，谢毅，毛裕民. 一条KRAB型锌指蛋白全长新基因的克隆与功能初探[J]. 遗传, 2000, 22(4): 247-251.
[14]	朱明华. 用PCR技术对原发性肝癌4号染色体标记的分析[J]. 遗传, 1994, 16(5): 17-19.