遗传 ›› 2012, Vol. 34 ›› Issue (3): 269-280.doi: 10.3724/SP.J.1005.2012.00269
许传铭, 万福生
收稿日期:2011-08-02
修回日期:2011-09-23
出版日期:2012-03-20
发布日期:2012-03-25
通讯作者:
万福生
E-mail:wanfs01@163.com
基金资助:江西省自然科学基金项目(编号：2010JZY0237)资助
XU Chuan-Ming, WAN Fu-Sheng
Received:2011-08-02
Revised:2011-09-23
Online:2012-03-20
Published:2012-03-25
摘要： Hippo信号通路是首次在果蝇中发现具有调节细胞增殖与凋亡作用的信号通路。最近发现果蝇Hippo信号通路的组成、分子作用机制和生物学功能在进化过程中高度保守。Hippo信号通路在胚胎发育中对细胞的生长分化、组织器官形成以及成体干细胞的维持和自稳态的保持等方面具有重要作用。同时, Hippo信号通路与Wnt信号通路、Notch信号通路等相互作用、密切联系, 在肿瘤的发生、发展过程中也起到关键作用。文章综述了哺乳动物Hippo信号通路的作用机理、与其他信号通路和蛋白质因子的相互联系及与肿瘤的关系, 对于肿瘤的诊断、预防和治疗具有一定的参考价值。
中图分类号:
许传铭，万福生. 哺乳动物Hippo信号通路：肿瘤治疗的新标靶[J]. 遗传, 2012, 34(3): 269-280.
XU Chuan-Ming, WAN Fu-Sheng. Hippo signaling pathway in mammals：a new therapeutic target for tumors[J]. HEREDITAS, 2012, 34(3): 269-280.
| [1] Huang JB, Wu S, Barrera J, Matthews K, Pan DJ. The Hippo signaling pathway coordinately regulates cell pro-liferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell, 2005, 122(3): 421-434.[2] Halder G, Johnson RL. Hippo signaling: growth control and beyond. Development, 2011, 138(1): 9-22.[3] Dong JX, Feldmann G, Huang JB, Wu S, 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.[4] 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.[5] Zhao B, Li L, Lei QY, Guan KL. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev, 2010, 24(9): 862-874.[6] Mao YP, Mulvaney J, Zakaria S, Yu T, Morgan KM, Allen S, Basson MA, Francis-West P, Irvine KD. Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development. Development, 2011, 138(5): 947-957.[7] Angus L, Moleirinho S, Herron L, Sinha A, Zhang X, Niestrata M, Dholakia K, Prystowsky MB, Harvey KF, Reynolds PA, Gunn-Moore FJ. Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP. Oncogene, 2011, 31(2): 238-250.[8] 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 on-coprotein to regulate tissue homeostasis in mammals. Dev Cell, 2010, 19(1): 27-38.[9] Xiao L, Chen YH, Ji M, Dong JX. KIBRA regulates Hippo signaling activity via interactions with large tumor suppressor kinases. J Biol Chem, 2011, 286(10): 7788-7796.[10] 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.[11] Luo XL, Hu JB, Li ZM, Yan Q, Li XL, Tao DD, Wang J, Leng Y, Gardner K, Judge SIV, Li QQ, Gong JP. The human WW45 protein enhances MST1-mediated apoptosis in vivo. Int J Mol Med, 2009, 23(3): 357-362.[12] Hergovich A, Schmitz D, Hemmings BA. The human tumour suppressor LATS1 is activated by human MOB1 at the membrane. Biochem Biophys Res Commun, 2006, 345(1): 50-58.[13] 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.[14] Morin-Kensicki EM, Boone BN, Howell M, Stonebraker JR, Teed J, Alb JG, Magnuson TR, O'Neal W, Milgram SL. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted dis-ruption of Yap65. Mol Cell Biol, 2006, 26(1): 77-87.[15] Makita R, Uchijima Y, Nishiyama K, Amano T, Chen Q, Takeuchi T, Mitani A, Nagase T, Yatomi Y, Aburatani H, Nakagawa O, Small EV, Cobo-Stark P, Igarashi P, Murakami M, Tominaga J, Sato T, Asano T, Kurihara Y, Kurihara H. Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. Am J Physiol Renal Physiol, 2008, 294(3): F542-F553.[16] 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.[17] Zhang H, Liu CY, Zha ZY, Zhao B, Yao J, Zhao S, Xiong Y, Lei QY, Guan KL. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesen- chymal transition. J Biol Chem, 2009, 284(20): 13355- 13362.[18] Pan DJ. The hippo signaling pathway in development and cancer. Dev Cell, 2010, 19(4): 491-505.[19] Glantschnig H, Rodan GA, Reszka AA. Mapping of MST1 kinase sites of phosphorylation. Activation and autophos-phorylation. J Biol Chem, 2002, 277(45): 42987-42996.[20] Das Thakur M, Feng YF, Jagannathan R, Seppa MJ, Skeath JB, Longmore GD. Ajuba LIM proteins are nega-tive regulators of the Hippo signaling pathway. Curr Biol, 2010, 20(7): 657-662.[21] Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, Oren M. The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev, 2010, 24(21): 2420-2429.[22] Vigneron AM, Ludwig RL, Vousden KH. Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes Dev, 2010, 24(21): 2430-2439.[23] Liu CY, Lv XB, Li TT, Xu YP, Zhou X, Zhao SM, Xiong Y, Lei QY, Guan KL. PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ. J Biol Chem, 2011, 286(7): 5558-5566.[24] Varelas X, Miller BW, Sopko R, Song SY, Gregorieff A, Fellouse FA, Sakuma R, Pawson T, Hunziker W, McNeill H, Wrana JL, Attisano L. The Hippo pathway regulates Wnt/β-catenin signaling. Dev Cell, 2010, 18(4): 579-591.[25] Hergovich A, Hemmings BA. TAZ-mediated crosstalk between Wnt and Hippo signaling. Dev Cell, 2010, 18(4): 508-509.[26] Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science, 2011, 332(6028): 458-461.[27] Xu Y, Stamenkovic I, Yu Q. CD44 attenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma. Cancer Res, 2010, 70(6): 2455-2464.[28] Fernandez-L A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM. YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev, 2009, 23(23): 2729-2741.[29] Yu JZ, Poulton J, Huang YC, Deng WM. The hippo path-way promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity. PLoS One, 2008, 3(3): e1761.[30] Kim D, Shu SK, Coppola MD, Kaneko S, Yuan ZQ, Cheng JQ. Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. PLoS One, 2010, 5(3): e9616.[31] Yuan ZQ, Kim D, Shu SK, Wu JB, Guo JP, Xiao L, Kaneko S, Coppola D, Cheng JQ. Phosphoinositide 3-kinase/ Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120. J Biol Chem, 2010, 285(6): 3815-3824.[32] O’Neill E, Kolch W. Taming the Hippo: Raf-1 controls apoptosis by suppressing MST2/Hippo. Cell Cycle, 2005, 4(3): 365-367.[33] Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem, 2003, 278(35): 33334-33341.[34] Qi C, Zhu YT, Hu LP, Zhu YJ. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers. Int J Cancer, 2009, 124(4): 793-798.[35] Striedinger K, VandenBerg SR, Baia GS, McDermott MW, Gutmann DH, Lal A. The neurofibromatosis 2 tumor suppressor gene product, merlin, regulates human meningioma cell growth by signaling through YAP. Neoplasia, 2008, 10(11): 1204-1212.[36] Morrison H, Sperka T, Manent J, Giovannini M, Ponta H, Herrlich P. Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac. Cancer Res, 2007, 67(2): 520-527.[37] Baser ME. The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene. Hum Mutat, 2006, 27(4): 297-306.[38] 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, 2010, 107(4): 1437-1442.[39] 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.[40] Steinmann K, Sandner A, Schagdarsurengin U, Dammann RH. Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma. Oncol Rep, 2009, 22(6): 1519-1526.[41] Seidel C, Schagdarsurengin U, Blümke K, Würl P, Pfeifer GP, Hauptmann S, Taubert H, Dammann R. Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma. Mol Carcinog, 2007, 46(10): 865-871.[42] Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass JR, Lugli A. Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. Mod Pathol, 2007, 20(3): 331-338.[43] Song JY, Lee JH, Joe CO, Lim DS, Chung JH. Retro-transposon-specific DNA hypomethylation and two-step loss-of-imprinting during WW45 haploinsuffi-ciency-induced hepatocarcinogenesis. Biochem Biophys Res Commun, 2011, 404(2): 728-734.[44] 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 prolif-eration, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA, 2010, 107(18): 8248-8253.[45] Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber DA, Hariharan IK. salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell, 2002, 110(4): 467-478.[46] Takahashi Y, Miyoshi Y, Takahata C, Irahara N, Taguchi T, Tamaki Y, Noguchi S. Down-regulation of LATS1 and LATS2 mRNA expression by promoter hy-permethylation and its association with biologically ag-gressive phenotype in human breast cancers. Clin Cancer Res, 2005, 11(4): 1380-1385.[47] Visser S, Yang XL. Identification of LATS transcriptional targets in HeLa cells using whole human genome oligonu-cleotide microarray. Gene, 2010, 449(1-2): 22-29.[48] Jiang Z, Li XG, Hu J, Zhou W, Jiang YQ, Li G, Lu DR. Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neurosci Res, 2006, 56(4): 450-458.[49] Lai ZC, Wei XM, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N, Ho LL, Li Y. Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell, 2005, 120(5): 675-685.[50] Sasaki H, Kawano O, Endo K, Suzuki E, Yukiue H, Ko-bayashi Y, Yano M, Fujii Y. Human MOB1 expression in non-small-cell lung cancer. Clin Lung Cancer, 2007, 8(4): 273-276.[51] Kosaka Y, Mimori K, Tanaka F, Inoue H, Watanabe M, Mori M. Clinical significance of the loss of MATS1 mRNA expression in colorectal cancer. Int J Oncol, 2007, 31(2): 333-338.[52] 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.[53] Steinhardt AA, Gayyed MF, Klein AP, Dong JX, Maitra A, Pan DJ, Montgomery EA, Anders RA. Expression of Yes-associated protein in common solid tumors. Hum Pathol, 2008, 39(11): 1582-1589.[54] Wang Y, Dong QZ, Zhang QF, Li ZX, Wang EH, Qiu XS. Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer. Cancer Sci, 2010, 101(5): 1279-1285.[55] Lam-Himlin DM, Daniels JA, Gayyed MF, Dong JX, Maitra A, Pan DJ, Montgomery EA, Anders RA. The hippo pathway in human upper gastrointestinal dysplasia and carcinoma: a novel oncogenic pathway. Int J Gas-trointest Cancer, 2006, 37(4): 103-109.[56] Chan SW, Lim CJ, Guo K, Ng CP, Lee I, Hunziker W, Zeng Q, Hong WJ. A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. Cancer Res, 2008, 68(8): 2592-2598.[57] Ren AX, Yan GJ, You B, Sun JX. Down-regulation of mammalian sterile 20-like kinase 1 by heat shock protein 70 mediates cisplatin resistance in prostate cancer cells. Cancer Res, 2008, 68(7): 2266-2274.[58] Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J, 1998, 17(8): 2224-2234.[59] Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S. MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. J Biol Chem, 2001, 276(22): 19276-19285.[60] Teraishi F, Guo W, Zhang LD, Dong FQ, Davis JJ, Sasa-zuki T, Shirasawa S, Liu JS, Fang BL. Activation of ster-ile20-like kinase 1 in proteasome inhibitor borte-zomib-induced apoptosis in oncogenic K-ras-transformed cells. Cancer Res, 2006, 66(12): 6072-6079.[61] Zhang JM, Smolen GA, Haber DA. Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway. Cancer Res, 2008, 68(8): 2789-2794.[62] Yang XL, Li DM, Chen WL, Xu T. Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G2/M arrest or apoptosis. Oncogene, 2001, 20(45): 6516-6523.[63] Li YF, Pei J, Xia H, Ke HG, Wang HY, Tao WF. Lats2, a putative tumor suppressor, inhibits G1/S transition. Oncogene, 2003, 22(28): 4398-4405.[64] Khazak V, Astsaturov I, Serebriiskii IG, Golemis EA. Selective Raf inhibition in cancer therapy. Expert Opin Ther Targets, 2007, 11(12): 1587-1609.[65] O'Neill E, Rushworth L, Baccarini M, Kolch W. Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science, 2004, 306(5705): 2267-2270.[66] Rudin CM, Marshall JL, Huang CH, Kindler HL, Zhang CB, Kumar D, Gokhale PC, Steinberg J, Wanaski S, Kasid UN, Ratain MJ. Delivery of a liposomal c-raf-1 antisense oligonucleotide by weekly bolus dosing in patients with advanced solid tumors: a Phase I study. Clin Cancer Res, 2004, 10(21): 7244-7251.[67] Cantor JP, Iliopoulos D, Rao AS, Druck T, Semba S, Han SY, McCorkell KA, Lakshman TV, Collins JE, Wachsber-ger P, Friedberg JS, Huebner K. Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity. Int J Cancer, 2007, 120(1): 24-31.[68] Dallol A, Agathanggelou A, Tommasi S, Pfeifer GP, Maher ER, Latif F. Involvement of the RASSF1A tumor suppressor gene in controlling cell migration. Cancer Res, 2005, 65(17): 7653-7659.[69] 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.[70] Liu AM, Poon RTP, Luk JM. MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties. Biochem Biophys Res Commun, 2010, 394(3): 623-627.[71] Liu X, Sempere LF, Ouyang HX, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by re-pressing specific tumor suppressors. J Clin Invest, 2010, 120(4): 1298-1309.[72] Cho WJ, Shin JM, Kim JS, Lee MR, Hong KS, Lee JH, Koo KH, Park JW, Kim KS. miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Mol Cells, 2009, 28(6): 521-527.[73] Hao YW, Chun A, Cheung K, Rashidi B, Yang XL. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem, 2008, 283(9): 5496-5509.[74] Monia BP, Sasmor H, Johnston JF, Freier SM, Lesnik EA, Muller M, Geiger T, Altmann KH, Moser H, Fabbro D. Sequence-specific antitumor activity of a phosphorothioate oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense mechanism of action in vivo. Proc Natl Acad Sci USA, 1996, 93(26): 15481-15484.[75] Gokhale PC, Zhang CB, Newsome JT, Pei J, Ahmad I, Rahman A, Dritschilo A, Kasid UN. Pharmacokinetics, toxicity, and efficacy of ends-modified raf an-tisense oligodeoxyribonucleotide encapsulated in a novel cationic liposome. Clin Cancer Res, 2002, 8(11): 3611-3621.[76] Dritschilo A, Huang CH, Rudin CM, Marshall J, Collins B, Dul JL, Zhang CB, Kumar D, Gokhale PC, Ahmad A, Ahmad I, Sherman JW, Kasid UN. Phase I study of lipo-some-encapsulated c-raf antisense oligodeoxyribonucleo-tide infusion in combination with radiation therapy in patients with advanced malignancies. Clin Cancer Res, 2006, 12(4): 1251-1259.[77] 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.[78] Zhang JM, Ji JY, Yu M, Overholtzer M, Smolen GA, Wang R, Brugge JS, Dyson NJ, Haber DA. YAP-dependent in-duction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat Cell Biol, 2009, 11(12): 1444-1450.[79] Zhao B, Wei XW, Li WQ, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu JS, Li L, Zheng P, Ye KQ, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP onco-protein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev, 2007, 21(21): 2747-2761.[80] Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, Gangeswaran R, Manson-Bishop C, Smith P, Danovi SA, Pardo O, Crook T, Mein CA, Lemoine NR, Jones LJ, Basu S. Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ, 2008, 15(11): 1752-1759.[81] Dornhöfer N, Spong S, Bennewith K, Salim A, Klaus S, Kambham N, Wong C, Kaper F, Sutphin P, Nacamuli R, Höckel M, Le Q, Longaker M, Yang G, Koong A, Giaccia A. Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res, 2006, 66(11): 5816-5827.[82] Zhang YX, Knyazev PG, Cheburkin YV, Sharma K, Knyazev YP, Õrfi L, Szabadkai I, Daub H, Kéri G, Ullrich A. AXL is a potential target for therapeutic intervention in breast cancer progression. Cancer Res, 2008, 68(6): 1905-1915.[83] Karp DD, Pollak MN, Cohen RB, Eisenberg PD, Haluska P, Yin D, Lipton A, Demers L, Leitzel K, Hixon ML, Ter-stappen LW, Garland L, Paz-Ares LG, Cardenal F, Langer CJ, Gualberto A. Safety, pharmacokinetics, and pharma-codynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751, 871) in combina-tion with paclitaxel and carboplatin. J Thorac On-col, 2009, 4(11): 1397-1403. |
| [1] | 程香荣,胡兴琳,姜琦,黄星卫,王楠,雷蕾. 核糖体DNA转录的表观调控与肿瘤发生[J]. 遗传, 2019, 41(3): 185-192. |
| [2] | 李鑫,李梦玮,张依楠,徐寒梅. 常用肿瘤基因分析方法及基于TCGA数据库的分析应用[J]. 遗传, 2019, 41(3): 234-242. |
| [3] | 吴保军,王卓,董宇,邓宇亮,施奇惠. 肺癌恶性胸腔积液中稀有肿瘤细胞的鉴定与单细胞测序分析[J]. 遗传, 2019, 41(2): 175-184. |
| [4] | 黎伟, 秦俊, 汪晖, 陈廖斌. 表观遗传生物标志物在人类疾病早期诊治中的研究进展[J]. 遗传, 2018, 40(2): 104-115. |
| [5] | 王天工, 叶孟. m 6A甲基化与肿瘤研究进展[J]. 遗传, 2018, 40(12): 1055-1065. |
| [6] | 孙书国, 吴世安, 张雷. Hippo信号通路在果蝇遗传学研究中的发现与扩展[J]. 遗传, 2017, 39(7): 537-545. |
| [7] | 吉新彦, 钟国轩, 赵斌. 哺乳动物Hippo信号通路分子机制研究进展[J]. 遗传, 2017, 39(7): 546-567. |
| [8] | 张平平,佟鑫,张天乐,黎子琛,龚清秋. 植物Hippo信号通路研究进展[J]. 遗传, 2017, 39(7): 568-575. |
| [9] | 顾远, 张雷, 余发星. Hippo信号通路在肠道稳态、再生及癌变过程中的作用及机制[J]. 遗传, 2017, 39(7): 588-596. |
| [10] | 付思玲,赵婉滢,张雯婧,宋海,季红斌,汤楠. Hippo信号通路在肺发育、再生和疾病中的功能[J]. 遗传, 2017, 39(7): 597-606. |
| [11] | 姚传波, 周鑫, 陈策实, 雷群英. Hippo信号通路在乳腺癌中的调控机制及作用[J]. 遗传, 2017, 39(7): 617-629. |
| [12] | 包笑妹, 何晴, 王莹, 黄智慧, 袁增强. Hippo/YAP信号通路在神经系统中的作用及机制研究进展[J]. 遗传, 2017, 39(7): 630-641. |
| [13] | 周欣,李伟芸,王红艳. MST1/2调控先天免疫的功能和机制[J]. 遗传, 2017, 39(7): 642-649. |
| [14] | 余淑娟,耿晶,陈兰芬. Hippo信号通路调控免疫细胞的功能[J]. 遗传, 2017, 39(7): 650-658. |
| [15] | 胡立桥,周兆才,田伟. Hippo信号通路结构生物学研究进展[J]. 遗传, 2017, 39(7): 659-674. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:
