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中华口腔医学研究杂志(电子版) ›› 2020, Vol. 14 ›› Issue (06) : 396 -400. doi: 10.3877/cma.j.issn.1674-1366.2020.06.010

所属专题: 口腔医学 文献

综述

Hippo信号通路在口腔鳞状细胞癌中的研究进展
易晨1, 黄子贤1, 余东升1,()   
  1. 1. 中山大学附属口腔医院,光华口腔医学院,广东省口腔医学重点实验室,广州 510055
  • 收稿日期:2020-02-19 出版日期:2020-12-01
  • 通信作者: 余东升

Research progress of Hippo signaling pathway in oral squamous cell carcinoma

Chen Yi1, Zixian Huang1, Dongsheng Yu1,()   

  1. 1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincal Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2020-02-19 Published:2020-12-01
  • Corresponding author: Dongsheng Yu
  • About author:
    Corresponding author: Yu Dongsheng, Email:
  • Supported by:
    National Natural Science Foundation of China(81873711, 82073378)
引用本文:

易晨, 黄子贤, 余东升. Hippo信号通路在口腔鳞状细胞癌中的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2020, 14(06): 396-400.

Chen Yi, Zixian Huang, Dongsheng Yu. Research progress of Hippo signaling pathway in oral squamous cell carcinoma[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2020, 14(06): 396-400.

口腔鳞状细胞癌(OSCC)是临床上最常见的头颈部鳞状细胞癌(HNSCC)之一,目前主要采用手术治疗为主、放化疗为辅,多种治疗方式联合的综合治疗方式来应对,由于其术后可能局部复发、淋巴结转移,患者术后5年生存率仍然不足50%,因此仍然需要寻找新的治疗方案。Hippo信号通路在调控器官大小、细胞数量和调节组织稳态平衡,以及在肿瘤的发生、发展中都发挥着至关重要的作用。研究表明,Hippo信号通路在调控OSCC细胞的增殖、侵袭和转移、凋亡和维持肿瘤干细胞特性等生物学行为中亦发挥着非常重要的作用。因此,Hippo信号通路可能为OSCC的治疗提供新的靶点。本文综述了Hippo信号通路的组成、调节机制及Hippo信号通路在OSCC发生、发展中的研究进展,以期为OSCC的研究和防治提供更广阔的思路。

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck squamous cell carcinomas. At present, the surgery is mainly used, the chemoradiotherapy as a supplement, and a variety of treatment methods combined to comprehensive therapy for the treatment of OSCC. However, the 5-year survival rate of OSCC is still less than 50% owing to local recurrence and lymph node metastasis, and we still need to find more new therapies. The Hippo signaling pathway plays a crucial role in regulating organ size, cell number and homeostasis, as well as in the development of tumors. Recent studies have shown that the Hippo signaling pathway also plays an important role in regulating the proliferation, invasion and metastasis, apoptosis of OSCC, and maintaining the characteristics of OSCC tumor stem cells, therefore, the Hippo signaling pathway may provide a new target for the treatment of OSCC. This paper reviews the composition and regulatory mechanism of Hippo signaling pathway and the research progress of Hippo signaling pathway in OSCC, which may provide a broader horizon for the research and treatment of OSCC.

[1]
Bray F, Ferlay J, Soerjomataram I,et al. Global cancer statistics 2018:Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin,2018,68(6):394-424. DOI:10.3322/caac.21492.
[2]
Biswas NK, Das C, Das S,et al. Lymph node metastasis in oral cancer is strongly associated with chromosomal instability and DNA repair defects [J]. Int J Cancer,2019,145(9):2568-2579. DOI:10.1002/ijc.32305.
[3]
Colevas AD, Yom SS, Pfister DG,et al. Nccn guidelines insights:Head and neck cancers,version 1.2018 [J]. J Natl Compr Canc Netw,2018,16(5):479-490. DOI:10.6004/jnccn.2018.0026.
[4]
Chai AWY, Lim KP, Cheong SC. Translational genomics and recent advances in oral squamous cell carcinoma [J]. Seminars in Cancer Biology,2020,61:71-83. DOI:10.1016/j.semcancer.2019.09.011.
[5]
Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control,tissue homeostasis,and cancer [J]. Cell,2015,163(4):811-828. DOI:10.1016/j.cell.2015.10.044.
[6]
Pan D. The hippo signaling pathway in development and cancer [J]. Dev Cell,2010,19(4):491-505. DOI:10.1016/j.devcel.2010.09.011.
[7]
Richardson HE, Portela M. Tissue growth and tumorigenesis in drosophila:Cell polarity and the hippo pathway [J]. Curr Opin Cell Biol,2017,48:1-9. DOI:10.1016/j.ceb.2017.03.006.
[8]
Snigdha K, Gangwani K, Lapalikar GV,et al. Hippo signaling in cancer:Lessons from drosophila models [J]. Front Cell Dev Biol,2019,7:85. DOI:10.3389/fcell.2019.00085.
[9]
Halder G, Johnson RL. Hippo signaling:Growth control and beyond [J]. Development,2011,138(1):9-22. DOI:10.1242/dev.045500.
[10]
Misra JR, Irvine KD. The hippo signaling network and its biological functions [J]. Annu Rev Genet,2018,52:65-87. DOI:10.1146/annurev-genet-120417-031621.
[11]
Dong JX, Feldmann G, Huang JB,et al. Elucidation of a universal size-control mechanism in drosophila and mammals [J]. Cell,2007,130(6):1120-1133. DOI:10.1016/j.cell.2007.07.019.
[12]
Fu V, Plouffe SW, Guan KL. The hippo pathway in organ development,homeostasis,and regeneration [J]. Curr Opin Cell Biol,2017,49:99-107. DOI:10.1016/j.ceb.2017.12.012.
[13]
Zhao B, Li L, Tumaneng K,et al. A coordinated phosphorylation by lats and ck1 regulates yap stability through scf beta-trcp [J]. Gene Dev,2010,24(1):72-85. DOI:10.1101/gad.1843810.
[14]
Lin KC, Park HW, Guan KL. Regulation of the hippo pathway transcription factor TEAD [J]. Trends Biochem Sci,2017,42(11):862-872. DOI:10.1016/j.tibs.2017.09.003.
[15]
Karaman R, Halder G. Cell junctions in hippo signaling [J]. Cold Spring Harb Perspect Biol,2018,10(5):a028753. DOI:10.1101/cshperspect.a028753.
[16]
Wu J, Minikes AM, Gao M,et al. Intercellular interaction dictates cancer cell ferroptosis via nf2-yap signalling [J]. Nature,2019,572(7769):402-406. DOI:10.1038/s41586-019-1426-6.
[17]
Meng Z, Moroishi T, Guan KL. Mechanisms of hippo pathway regulation [J]. Genes Dev,2016,30(1):1-17. DOI:10.1101/gad.274027.115.
[18]
Wang X, Zhang Y, Blair SS. Fat-regulated adaptor protein dlish binds the growth suppressor expanded and controls its stability and ubiquitination [J]. Proc Natl Acad Sci U S A,2019,116(4):1319-1324. DOI:10.1073/pnas.1811891116.
[19]
Luo J, Yu FX. Gpcr-hippo signaling in cancer [J]. Cells,2019,8(5):4256. DOI:10.3390/cells8050426.
[20]
Ardestani A, Lupse B, Maedler K. Hippo signaling:Key emerging pathway in cellular and whole-body metabolism [J]. Trends Endocrinol Metab,2018,29(7):492-509. DOI:10.1016/j.tem.2018.04.006.
[21]
Zanconato F, Cordenonsi M, Piccolo S. Yap/taz at the roots of cancer [J]. Cancer Cell,2016,29(6):783-803. DOI:10.1016/j.ccell.2016.05.005.
[22]
Zhao B, Li L, Wang L,et al. Cell detachment activates the hippo pathway via cytoskeleton reorganization to induce anoikis [J]. Genes Dev,2012,26(1):54-68. DOI:10.1101/gad.173435.111.
[23]
Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation [J]. Cell,2011,144(5):646-674. DOI:10.1016/j.cell.2011.02.013.
[24]
Zhang L, Ye DX, Pan HY,et al. Yes-associated protein promotes cell proliferation by activating fos related activator-1 in oral squamous cell carcinoma [J]. Oral Oncol,2011,47(8):693-697. DOI:10.1016/j.oraloncology.2011.06.003.
[25]
Chen X, Gu W, Wang Q,et al. C-myc and bcl-2 mediate yap-regulated tumorigenesis in oscc [J]. Oncotarget,2018,9(1):668-679. DOI:10.18632/oncotarget.23089.
[26]
Ge L, Smail M, Meng W,et al. Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis [J]. PLoS One,2011,6(11):e27529. DOI:10.1371/journal.pone.0027529.
[27]
Wei Z, Wang Y, Li Z,et al. Overexpression of hippo pathway effector taz in tongue squamous cell carcinoma:Correlation with clinicopathological features and patients′ prognosis [J]. J Oral Pathol Med,2013,42(10):747-754. DOI:10.1111/jop.12062.
[28]
Dong C, Wei KJ, Zhang WB,et al. Lats2 induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating yap in oral squamous cell carcinoma [J]. J Oral Pathol Med,2015,44(6):475-481. DOI:10.1111/jop.12317.
[29]
Hiemer SE, Zhang L, Kartha VK,et al. A YAP/TAZ-regulated molecular signature is associated with oral squamous cell carcinoma [J]. Mol Cancer Res,2015,13(6):957-968. DOI:10.1158/1541-7786.Mcr-14-0580.
[30]
Su L, Wang S, Yuan T,et al. Anti-oral squamous cell carcinoma effects of a potent taz inhibitor ar-42 [J]. Journal of Cancer,2020,11(2):364-373. DOI:10.7150/jca.32436.
[31]
Ma C, Fan L, Wang J,et al. Hippo/Mst1 overexpression induces mitochondrial death in head and neck squamous cell carcinoma via activating β-catenin/Drp1 pathway [J]. Cell Stress and Chaperones,2019,24(4):807-816. DOI:10.1007/s12192-019-01008-9.
[32]
Pindiprolu S, Krishnamurthy PT, Chintamaneni PK. Pharmacological targets of breast cancer stem cells:A review [J]. Naunyn Schmiedebergs Arch Pharmacol,2018,391(5):463-479. DOI:10.1007/s00210-018-1479-3.
[33]
Skvortsov S, Skvortsova, II, Tang DG,et al. Concise review:prostate cancer stem cells:current understanding [J]. Stem Cells,2018,36(10):1457-1474. DOI:10.1002/stem.2859.
[34]
Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression [J]. J Biomed Sci,2018,25(1):20. DOI:10.1186/s12929-018-0426-4.
[35]
Basu-Roy U, Bayin NS, Rattanakorn K,et al. Sox2 antagonizes the hippo pathway to maintain stemness in cancer cells [J]. Nature Communications,2015,6:6411. DOI:10.1038/ncomms7411.
[36]
Li Z, Wang Y, Zhu Y,et al. The hippo transducer TAZ promotes epithelial to mesenchymal transition and cancer stem cell maintenance in oral cancer [J]. Mol Oncol,2015,9(6):1091-1105. DOI:10.1016/j.molonc.2015.01.007.
[37]
Li J, Li Z, Wu Y,et al. The Hippo effector TAZ promotes cancer stemness by transcriptional activation of SOX2 in head neck squamous cell carcinoma [J]. Cell Death & Disease,2019,10:603. DOI:10.1038/s41419-019-1838-0.
[38]
Cordenonsi M, Zanconato F, Azzolin L,et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells [J]. Cell,2011,147(4):759-772. DOI:10.1016/j.cell.2011.09.048.
[39]
Lai D, Ho KC, Hao Y,et al. Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF [J]. Cancer Res,2011,71(7):2728-2738. DOI:10.1158/0008-5472.CAN-10-2711.
[40]
Lin L, Sabnis AJ, Chan E,et al. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies [J]. Nat Genet,2015,47(3):250-256. DOI:10.1038/ng.3218.
[41]
Zhou X, Wang S, Wang Z,et al. Estrogen regulates Hippo signaling via GPER in breast cancer [J]. J Clin Invest,2015,125(5):2123-2135. DOI:10.1172/JCI79573.
[42]
Yoshikawa K, Noguchi K, Nakano Y,et al. The Hippo pathway transcriptional co-activator,YAP,confers resistance to cisplatin in human oral squamous cell carcinoma [J]. Int J Oncol,2015,46(6):2364-2370. DOI:10.3892/ijo.2015.2948.
[43]
Attisano L, Wrana JL. Signal integration in TGF-β,WNT,and Hippo pathways [J]. F1000Prime Rep,2013,5:17. DOI:10.12703/P5-17.
[44]
Bernascone I, Martin-Belmonte F. Crossroads of Wnt and Hippo in epithelial tissues [J]. Trends Cell Biol,2013,23(8):380-389. DOI:10.1016/j.tcb.2013.03.007.
[45]
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. DOI:10.1038/ncb1748.
[46]
Azzolin L, Panciera T, Soligo S,et al. YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response [J]. Cell,2014,158(1):157-170. DOI:10.1016/j.cell.2014.06.013.
[47]
Mohseni M, Sun J, Lau A,et al. A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway [J]. Nat Cell Biol,2014,16(1):108-117. DOI:10.1038/ncb2884.
[48]
García-Escudero R, Segrelles C, Dueñas M,et al. Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway [J]. Oral Oncology,2018,79:55-63. DOI:10.1016/j.oraloncology.2018.02.014.
[49]
Zanconato F, Battilana G, Cordenonsi M,et al. YAP/TAZ as therapeutic targets in cancer [J]. Curr Opin Pharmacol,2016,29:26-33. DOI:10.1016/j.coph.2016.05.002.
[50]
Liu-Chittenden Y, Huang B, Shim JS,et al. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP [J]. Genes Dev,2012,26(12):1300-1305. DOI:10.1101/gad.192856.112.
[51]
Jiao S, Wang H, Shi Z,et al. A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer [J]. Cancer Cell,2014,25(2):166-180. DOI:10.1016/j.ccr.2014.01.010.
[52]
Bao Y, Nakagawa K, Yang Z,et al. A cell-based assay to screen stimulators of the Hippo pathway reveals the inhibitory effect of dobutamine on the YAP-dependent gene transcription [J]. J Biochem,2011,150(2):199-208. DOI:10.1093/jb/mvr063.
[53]
Yu FX, Guan KL. The Hippo pathway:regulators and regulations [J]. Gene Dev,2013,27(4):355-371. DOI:10.1101/gad.210773.112.
[54]
Ji L, Liu C, Yuan Y,et al. Key roles of rho GTPases,YAP,and Mutant p53 in anti-neoplastic effects of statins [J]. Fundam Clin Pharmacol,2020,34(1):4-10. DOI:10.1111/fcp.12495.
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