Role of the Hippo signaling pathway in the development and progression of primary liver cancer

Hong YingHui; Wang Chun; Ye MingLiang; Luo Jie; Liu JiaLiang; Ren Chao; Lan SiYu; Zhao Qiu; Chang Ying

doi:10.3969/j.issn.1001-5256.2020.05.050

Volume 36 Issue 5

May 2020

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Article Navigation > Journal of Clinical Hepatology > 2020 > 36(5): 1171-1174

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Role of the Hippo signaling pathway in the development and progression of primary liver cancer

DOI: 10.3969/j.issn.1001-5256.2020.05.050

Hubei Key Laboratory of Intestinal and Colorectal Diseases, Hubei Clinical Center of Intestinal and Colorectal Diseases, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

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Published Date: 2020-05-20

Abstract

Abstract

The incidence rate of primary liver cancer continues to increase around the world, with a younger age of onset and poorer prognosis. As the most classic regulator of cell polarity and density, mechanical signal transduction, cell proliferation, and organ development, the Hippo pathway can promote the development and progression of various cancers including primary liver cancer. YAP, a classic nuclear effector of the Hippo pathway, is significantly upregulated in primary liver cancer and promotes the development of drug resistance. This article aims to investigate the association of the dysregulation of the Hippo signaling pathway with the development and progression of primary liver cancer and analyzes the mechanism of action of the Hippo signaling pathway in the drug resistance of primary liver cancer as an early event of the development of primary liver cancer, which is of great significance for exploring new treatment strategies for primary liver cancer.
- liver neoplasms,
- signal transduction,
- Hippo pathway

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References(40)

References

[1] RAWLA P, SUNKARA T, MURALIDHARAN P, et al. Update in global trends and aetiology of hepatocellular carcinoma[J].Contemp Oncol(Pozn), 2018, 22(3):141-150.

[2] WANG Y, DONG Q, ZHANG Q, et al. Overexpression of yesassociated protein contributes to progression and poor prognosis of non-small-cell lung cancer[J]. Cancer Sci, 2010, 101(5):1279-1285.

[3] 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.

[4] YANG Y, WU QJ, XIE L, et al. Prospective cohort studies of association between family history of liver cancer and risk of liver cancer[J]. Int J Cancer, 2014, 135(7):1605-1614.

[5] OTA M, SASAKI H. Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling[J]. Development, 2008, 135(24):4059-4069.

[6] ZHAO B, WEI X, LI W, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control[J]. Genes Dev, 2007, 21(21):2747-2761.

[7] HALDER G, JOHNSON RL. Hippo signaling:Growth control and beyond[J]. Development, 2011, 138(1):9-22.

[8] ZANCONATO F, BATTILANA G, CORDENONSI M, et al. YAP/TAZ as therapeutic targets in cancer[J]. Curr Opin Pharmacol,2016, 29:26-33.

[9] ZHU C, LI L, ZHAO B. The regulation and function of YAP transcription co-activator[J]. Acta Biochim Biophys Sin(Shanghai), 2015, 47(1):16-28.

[10] MACIAS MJ, HYVÖNEN M, BARALDI E, et al. Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide[J]. Nature, 1996, 382(6592):646-649.

[11] YAGI R, CHEN LF, SHIGESADA K, et al. A WW domaincontaining yes-associated protein(YAP)is a novel transcriptional co-activator[J]. EMBO J, 1999, 18(9):2551-2562.

[12] OKA T, REMUE E, MEERSCHAERT K, et al. Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling[J].Biochem J, 2010, 432(3):461-472.

[13] KOWALIK MA, SALIBA C, PIBIRI M, et al. Yes-associated protein regulation of adapative liver enlargement and hepatocellular carcinoma development in mice[J]. Hepatology,2011, 53(6):2086-2096.

[14] MOON S, KIM W, KIM S, et al. Phosphorylation by NLK inhibits YAP-14-3-3-interactions and induces its nuclear localization[J]. EMBO Rep, 2017, 18(1):61-71.

[15] LIU CY, ZHA ZY, ZHOU X, et al. The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase[J]. J Biol Chem, 2010, 285(48):37159-37169.

[16] HANSEN CG, MOROISHI T, GUAN KL. YAP and TAZ:A nexus for Hippo signaling and beyond[J]. Trends Cell Biol,2015, 25(9):499-513.

[17] MOROISHI T, HANSEN CG, GUAN KL. The emerging roles of YAP and TAZ in cancer[J]. Nat Rev Cancer, 2015, 15(2):73-79.

[18] MOYA IM, HALDER G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine[J]. Nat Rev Mol Cell Biol, 2019, 20(4):211-226.

[19] GUO LW, SHAO GL, LUO J, et al. YAP regulates the proliferation and modifies the sensitivity to sorafenib in hepatocellular carcinoma cells[J]. Chin J Oncol, 2018, 40(11):818-823.(in Chinese）郭立文，邵国良，罗君，等．YAP调控肝癌细胞增殖活性及对索拉非尼敏感性的影响[J]．中华肿瘤杂志，2018, 40(11):818-823.

[20] BÖTTCHER K, PINZANI M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents[J]. Adv Drug Deliv Rev, 2017, 121:3-8.

[21] ZAGHARI Z, AZIZIAN J. Synthesis of novelα-amidino carboxylic acids and their use as H-Bond catalysts in strecker reaction[J]. Comb Chem High Throughput Screen, 2018, 21(8):609-614.

[22] de OLIVEIRA DA SILVA B, RAMOS LF, MORAES K. Molecular interplays in hepatic stellate cells:Apoptosis, senescence,and phenotype reversion as cellular connections that modulate liver fibrosis[J]. Cell Biol Int, 2017, 41(9):946-959.

[23] DUPONT S, MORSUT L, ARAGONA M, et al. Role of YAP/TAZ in mechanotransduction[J]. Nature, 2011, 474(7350):179-183.

[24] MANNAERTS I, LEITE SB, VERHULST S, et al. The Hippo pathway effector YAP controls mouse hepatic stellate cell activation[J]. J Hepatol, 2015, 63(3):679-688.

[25] KIM W, KHAN SK, GVOZDENOVIC-JEREMIC J, et al. Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis[J]. J Clin Invest, 2017,127(1):137-152.

[26] MOON H, CHO K, SHIN S, et al. High risk of hepatocellular carcinoma development in fibrotic liver:Role of the HippoYAP/TAZ signaling pathway[J]. Int J Mol Sci, 2019, 20(3):581-583.

[27] LIN TH, SHAO YY, CHAN SY, et al. High serum transforming growth factor-β1 levels predict outcome in hepatocellular carcinoma patients treated with sorafenib[J]. Clin Cancer Res,2015, 21(16):3678-3684.

[28] FERRIGNO O, LALLEMAND F, VERRECCHIA F, et al. Yesassociated protein(YAP65)interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling[J]. Oncogene, 2002, 21(32):4879-4884.

[29] LIU F, LAGARES D, CHOI KM, et al. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis[J]. Am J Physiol Lung Cel Mol Physiol, 2015, 308(4):L344-357.

[30] VARELAS X, SAMAVARCHI-TEHRANI P, NARIMATSU M, et al.The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway[J]. Dev Cell,2010, 19(6):831-844.

[31] de LA COSTE A, ROMAGNOLO B, BILLUART P, et al. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas[J]. Proc Natl Acad Sci U S A, 1998, 95(15):8847-8851.

[32] BARTEL DP. MicroRNAs:Target recognition and regulatory functions[J]. Cell, 2009, 136(2):215-233.

[33] LIU AM, POON RT, LUK JM. MicroRNA-375 targets Hipposignaling effector YAP in liver cancer and inhibits tumor properties[J]. Biochem Biophys Res Commun, 2010, 394(3):623-627.

[34] HAN LL, YIN XR, ZHANG SQ. miR-103 promotes the metastasis and EMT of hepatocellular carcinoma by directly inhibiting LATS2[J]. Int J Oncol, 2018, 53(6):2433-2444.

[35] RUAN T, HE X, YU J, et al. MicroRNA-186 targets Yes-associated protein 1 to inhibit Hippo signaling and tumorigenesis in hepatocellular carcinoma[J]. Oncol Lett, 2016, 11(4):2941-2945.

[36] LIU P, ZHANG H, LIANG X, et al. HBV preS2 promotes the expression of TAZ via miRNA-338-3p to enhance the tumorigenesis of hepatocellular carcinoma[J]. Oncotarget, 2015, 6(30):29048-29059.

[37] WU H, ZHANG W, WU Z, et al. miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocel ular carcinoma[J]. Cel Death Dis, 2019, 10(2):48.

[38] KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma:A randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126):1163-1173.

[39] CUI YL. Targeted therapy for hepatocellular carcinoma[J].Chin J Dig Surg, 2018, 17(5):445-451.(in Chinese）崔云龙．肝癌的靶向治疗[J]．中华消化外科杂志，2018, 17(5):445-451.

[40] GAO J, RONG Y, HUANG Y, et al. Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP[J]. J Cell Physiol, 2019,234(3):2639-2648.

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沈阳化工大学材料科学与工程学院沈阳 110142

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Role of the Hippo signaling pathway in the development and progression of primary liver cancer

DOI: 10.3969/j.issn.1001-5256.2020.05.050