山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (3): 111-117.doi: 10.6040/j.issn.1673-3770.0.2022.147

• 综述 • 上一篇    

线粒体自噬与头颈部鳞状细胞癌关系的研究进展

索安奇1,杨欣欣2   

  1. 1. 济宁医学院 临床医学院, 山东 济宁 272007;
    2. 济宁医学院附属医院 耳鼻咽喉头颈外科, 山东 济宁 272007
  • 发布日期:2023-05-24
  • 通讯作者: 杨欣欣. E-mail:yangjnmc@163.com
  • 基金资助:
    济宁医学院贺林基金项目(JYHL2018FMS09);济宁医学院科研扶持基金项目(JYFC2018FKJ133);山东省中医药管理局山东省中医药科技发展计划项目(2019-0495)

Research progress on the relationship between mitochondrial autophagy and squamous cell carcinoma of the head and neck

SUO Anqi1, YANG Xinxin2   

  1. 1. School of Clinical Medical, Jining Medical University, Jining 272007, Shandong, China;
    2. Department of Otorhinolaryngology & Head and Neck Surgery, Affiliated Hospital of Jining Medical University, Jining 272007, Shandong, China
  • Published:2023-05-24

摘要: 头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)是全球最常见的6种癌症之一,很多晚期患者因肿瘤复发或对化疗药物耐药而死亡。努力开拓治疗HNSCC新策略,对于HNSCC患者的预后具有重大意义。线粒体自噬是一种选择性的宏观自噬形式,通过相关通路蛋白或者药物调控减轻氧化应激和预防癌的发生,又或者在一些不利条件下促进肿瘤细胞的存活。目前大量研究证明,线粒体自噬是控制癌细胞质量的关键因素,与肿瘤发生发展密切相关。线粒体功能障碍促进细胞癌变;线粒体自噬功能失调可诱导癌细胞凋亡;新型药物的出现开拓了靶向线粒体治疗肿瘤的新方法,线粒体自噬对于肿瘤的防治展现出巨大潜能。论文将从线粒体自噬的调控机制、线粒体自噬与肿瘤的关系、HNSCC防治及临床耐药性等方面进行综述,旨在为HNSCC治疗提供新的方向和靶点。

关键词: 线粒体自噬, 头颈部鳞状细胞癌, 氧化应激, 线粒体功能障碍, 调控机制, 临床耐药性

Abstract: Head and neck squamous cell carcinoma(HNSCC)is among the six most common cancers worldwide. Many patients in advanced stages of HNSCC die because of tumor recurrence or resistance to chemotherapy drugs. New treatment strategies are needed to improve the prognosis of HNSCC patients. Mitochondrial autophagy is a selective form of macro autophagy which reduces oxidative stress and prevents cancer by regulating related pathway proteins or drugs, or by promoting the survival of tumor cells under some adverse conditions. Mitochondrial autophagy is the key factor to control the quality of cancer cells which is closely related to the occurrence and development of cancer. Mitochondrial dysfunction promotes cell carcinogenesis, and mitochondrial autophagy dysfunction can induce apoptosis of cancer cells. The discovery and development of new drugs has created new options in targeting mitochondria to treat tumors. Mitochondrial autophagy shows great potential for the prevention and treatment of tumors. This article reviews the regulatory mechanism of mitochondrial autophagy, relationship between mitochondrial autophagy and tumor, and prevention and treatment of HNSCC and clinical drug resistance. The aim of this study is to provide new research directions and targets for the treatment of HNSCC.

Key words: Mitochondrial autophagy, Head and neck squamous cell carcinoma, Oxidative stress, Mitochondrial dysfunction, Regulatory mechanism, Clinical resistance

中图分类号: 

  • R739.9
[1] 胡晨, 薛继尧, 龚洪立, 等. 喉鳞状细胞癌局部复发影响因素及预后分析[J]. 临床耳鼻咽喉头颈外科杂志, 2020, 34(9): 773-776. doi:10.13201/j.issn.2096-7993.2020.09.002 HU Chen, XUE Jiyao, GONG Hongli, et al. Analysis of correlation factors and prognosis of local recurrence of laryngeal squamous cell carcinoma[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2020, 34(9): 773-776. doi:10.13201/j.issn.2096-7993.2020.09.002
[2] Luo M, Sun G, Sun JW. miR-196b affects the progression and prognosis of human LSCC through targeting PCDH-17[J]. Auris Nasus Larynx, 2019, 46(4): 583-592. doi:10.1016/j.anl.2018.10.020
[3] 王媚, 李志海. 喉癌干细胞:克服多药耐药性的潜在治疗靶点[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 120-128. doi: 10.6040/j.issn.1673-3770.0.2021.388 WANG Mei, LI Zhihai. Laryngeal cancer stem cells: potential therapeutic targets for overcoming multidrug resistance[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 120-128. doi: 10.6040/j.issn.1673-3770.0.2021.388
[4] Liu C, Yu Z, Huang S, et al. Combined identification of three miRNAs in serum as effective diagnostic biomarkers for HNSCC[J]. EBioMedicine, 2019, 50: 135-143. doi:10.1016/j.ebiom.2019.11.016
[5] Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: an overview[J]. Int J Cancer, 2021, 5(149):778-789. doi:10.1002/ijc.33588
[6] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi:10.3322/caac.21660
[7] Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance[J]. Curr Biol, 2018, 28(4): R170-R185. doi:10.1016/j.cub.2018.01.004
[8] Fan P, Xie XH, Chen CH, et al. Molecular regulation mechanisms and interactions between reactive oxygen species and mitophagy[J]. DNA Cell Biol, 2019, 38(1): 10-22. doi:10.1089/dna.2018.4348
[9] Moro L. Mitochondrial dysfunction in aging and cancer[J]. J Clin Med, 2019, 8(11): 1983. doi:10.3390/jcm8111983
[10] 李丹, 李翀, 蒋敬庭. 自噬在肿瘤发生与发展中的调控机制[J]. 临床肿瘤学杂志, 2013, 18(6): 561-564. doi:10.3969/j.issn.1009-0460.2013.06.019 LI Dan, LI Chong, JIANG Jingting. The regulatory mechanism of autophagy in tumorigenesis and development[J]. Chinese Clinical Oncology, 2013, 18(6): 561-564. doi:10.3969/j.issn.1009-0460.2013.06.019
[11] Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective[J]. Cell, 2019, 176(1/2): 11-42. doi:10.1016/j.cell.2018.09.048
[12] Matsuda N, Sato S, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy[J]. J Cell Biol, 2010, 189(2): 211-221. doi:10.1083/jcb.200910140
[13] Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease[J]. Neuron, 2015, 85(2): 257-273. doi:10.1016/j.neuron.2014.12.007
[14] Skoda J, Borankova K, Jansson PJ, et al. Pharmacological targeting of mitochondria in cancer stem cells: an ancient organelle at the crossroad of novel anti-cancer therapies[J]. Pharmacol Res, 2019, 1(139): 298-313. doi:10.1016/j.phrs.2018.11.020
[15] Seirafi M, Kozlov G, Gehring K. Parkin structure and function[J]. FEBS J, 2015, 282(11): 2076-2088. doi:10.1111/febs.13249
[16] Lee JY, Nagano Y, Taylor JP, et al. Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy[J]. J Cell Biol, 2010, 189(4): 671-679. doi:10.1083/jcb.201001039
[17] 路云萍, 李玲玉, 景新颖, 等. Prx1调控PINK1/Parkin介导的线粒体自噬在实验性口腔黏膜癌变中的作用[J]. 北京口腔医学, 2021, 29(1): 1-6. LU Yunping, LI Lingyu, JING Xinying, et al. Peroxiredoxin 1 regulates PINK1/parkin-mediated mitophagy in 4NQO-induced oral carcinogenesis[J]. Beijing Journal of Stomatology, 2021, 29(1): 1-6.
[18] Hoshino A, Ariyoshi M, Okawa Y, et al. Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic β-cell function in diabetes[J]. PNAS, 2014, 111(8): 3116-3121. doi:10.1073/pnas.1318951111
[19] 何云凌. 低氧下BNIP3翻译后修饰对线粒体自噬的调控作用[C]. 北京:军事科学院, 2018.
[20] Regula KM, Ens K, Kirshenbaum LA. Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes[J]. Circ Res, 2002, 91(3): 226-231. doi:10.1161/01.res.0000029232.42227.16
[21] Hamacher-Brady A, Brady NR, Logue SE, et al. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy[J]. Cell Death Differ, 2007, 14(1): 146-157. doi:10.1038/sj.cdd.4401936
[22] Zhang H, Bosch-Marce M, Shimoda LA, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia[J]. J Biol Chem, 2008, 283(16): 10892-10903. doi:10.1074/jbc.M800102200
[23] Bellot G, Garcia-Medina R, Gounon P, et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains[J]. Mol Cell Biol, 2009, 29(10): 2570-2581. doi:10.1128/MCB.00166-09
[24] Semenza GL. Hypoxia-inducible factors in physiology and medicine[J]. Cell, 2012, 148(3): 399-408. doi:10.1016/j.cell.2012.01.021
[25] Hanna RA, Quinsay MN, Orogo AM, et al. Microtubule-associated protein 1 light chain 3(LC3)interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy[J]. J Biol Chem, 2012, 287(23): 19094-19104. doi:10.1074/jbc.M111.322933
[26] Novak I, Kirkin V, McEwan DG, et al. Nix is a selective autophagy receptor for mitochondrial clearance[J]. EMBO Rep, 2010, 11(1): 45-51. doi:10.1038/embor.2009.256
[27] Shaid S, Brandts CH, Serve H, et al. Ubiquitination and selective autophagy[J]. Cell Death Differ, 2013, 20(1): 21-30. doi:10.1038/cdd.2012.72
[28] 郭倩, 王蓓. 低氧诱导线粒体自噬的机制及其在相关疾病中的研究进展[J]. 国际呼吸杂志, 2018, 38(8): 610-614. doi:10.3760/cma.j.issn.1673-436X.2018.08.009 GUO Qian, WANG Bei. Mechanisms of hypoxia-induced mitophagy and its advances in related diseases[J]. Int J Respir, 2018, 38(8): 610-614. doi:10.3760/cma.j.issn.1673-436X.2018.08.009
[29] You L, Wang Z, Li H, et al. The role of STAT3 in autophagy[J]. Autophagy, 2015, 11(5): 729-739. doi:10.1080/15548627.2015.1017192
[30] Sun W, Wang B, Qu XL, et al. Metabolism of reactive oxygen species in osteosarcoma and potential treatment applications[J]. Cells, 2019, 9(1): 87. doi:10.3390/cells9010087
[31] 唐笑怡, 张攀, 王凯燕, 等. 线粒体功能与口腔鳞状细胞癌关系的研究进展[J]. 口腔疾病防治, 2022, 30(3): 212-216. doi:10.12016/j.issn.2096-1456.2022.03.009 TANG Xiaoyi, ZHANG Pan, WANG Kaiyan, et al. Research progress on the relationship between mitochondrial function and oral squamous cell carcinoma[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2022, 30(3): 212-216. doi:10.12016/j.issn.2096-1456.2022.03.009
[32] Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene[J]. J Clin Invest, 2003, 112(12): 1809-1820. doi:10.1172/JCI20039
[33] Pirtoli L, Cevenini G, Tini P, et al. The prognostic role of Beclin 1 protein expression in high-grade gliomas[J]. Autophagy, 2009, 5(7): 930-936. doi:10.4161/auto.5.7.9227
[34] Ding ZB, Shi YH, Zhou J, et al. Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma[J]. Cancer Res, 2008, 68(22): 9167-9175. doi:10.1158/0008-5472.CAN-08-1573
[35] Yu M, Gou WF, Zhao S, et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas[J]. Tumour Biol, 2013, 34(2): 1071-1083. doi:10.1007/s13277-013-0648-8
[36] 黄莉. 自噬相关基因Beclin 1在喉鳞状细胞癌中的表达及意义[D]. 长沙: 中南大学, 2008.
[37] Liu K, Lee J, Kim JY, et al. Mitophagy controls the activities of tumor suppressor p53 to regulate hepatic cancer stem cells[J]. Mol Cell, 2017, 68(2): 281-292.e5. doi:10.1016/j.molcel.2017.09.022
[38] 刘腾飞. MS-275联合顺铂对食管鳞癌的抗肿瘤作用[D]. 郑州: 郑州大学, 2019.
[39] Naik PP, Mukhopadhyay S, Panda PK, et al. Autophagy regulates cisplatin-induced stemness and chemoresistance via the upregulation of CD44, ABCB1 and ADAM17 in oral squamous cell carcinoma[J]. Cell Prolif, 2018, 51(1): e12411. doi:10.1111/cpr.12411
[40] 胡静, 苏荣健, 赵子明, 等. 自噬介导人舌鳞癌细胞对顺铂耐药的作用及其机制研究[J]. 医学与哲学(B), 2015, 36(6): 65-67. HU Jing, SU Rongjian, ZHAO Ziming, et al. The study on the role of human tongue squamous cell cancer cells resistance to cisplatin mediated autophagy and its mechanism[J]. Medicine & Philosophy(B), 2015, 36(6): 65-67.
[41] 金香顺, 王东旭, 尤涛. 抑制自噬可以增加mTOR抑制剂AZD8055引起的喉癌细胞株Hep-2的凋亡[J]. 中国老年学杂志, 2015, 35(14): 3847-3849. doi: 10.3969/j.issn.1005-9202.2015.14.023
[42] 王荣坤, 林简. 3-甲基腺嘌呤增强ALA-PDT对皮肤鳞状细胞癌A431细胞的杀伤作用[J]. 中国皮肤性病学杂志, 2020, 34(6): 627-633. doi:10.13735/j.cjdv.1001-7089.201908164 WANG Rongkun, LIN Jian. 3-methyladenine enhances the killing effect of ALA-PDT on cutaneous squamous cell carcinoma A431 cells[J]. The Chinese Journal of Dermatovenereology, 2020, 34(6): 627-633. doi:10.13735/j.cjdv.1001-7089.201908164
[43] 谢章弘, 华清泉. 铁死亡在头颈部鳞状细胞癌中的研究进展[J]. 肿瘤防治研究, 2022, 49(4): 282-287. doi:10.3971/j.issn.1000-8578.2021.21.1117 XIE Zhanghong, HUA Qingquan. Research progress of ferroptosis in head and neck squamous cell carcinoma[J]. Cancer Research on Prevention and Treatment, 2022, 49(4): 282-287. doi:10.3971/j.issn.1000-8578.2021.21.1117
[1] 艾自琴,李军政. 免疫疫苗在头颈部鳞状细胞癌中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 143-150.
[2] 李孟婷,何书喜,王华. 炎症因子在圆锥角膜中的研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(2): 151-158.
[3] 苏杰,杨馥宇,李猛,陈荟茹,蒋利生,王丽香. GLP-1诱导的自噬对糖尿病大鼠视网膜病变的保护作用[J]. 山东大学耳鼻喉眼学报, 2022, 36(5): 30-34.
[4] 张依,王文俊,杨安怀. SIRT1激动剂白藜芦醇在眼部疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 151-156.
[5] 付奕豪,徐逸轩,严宏,张婕. 谷氧还蛋白在眼病中的作用研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(3): 125-130.
[6] 于克娜,孙凯月,张杰,金鹏. 西妥昔单抗治疗头颈部鳞状细胞癌差异表达基因的生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(4): 117-124.
[7] 宋凡,黄炜峻,许华俊,关建,易红良. 阻塞性睡眠呼吸暂停综合征患者颈动脉弹性与氧化应激反应的关系[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 99-104.
[8] 吴静,刘业海. 头颈部鳞状细胞癌的靶向治疗研究进展[J]. 山东大学耳鼻喉眼学报, 2018, 32(5): 97-102.
[9] 张转,刘涛,白治丽,周长明. 氧化应激与噪音性聋发病机制及治疗进展[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 101-103.
[10] 李小波,曹忠胜,辛洁,谢辰,陈锐. 罗格列酮对间歇性低氧小鼠氧化应激及认知功能的作用研究[J]. 山东大学耳鼻喉眼学报, 2017, 31(1): 45-49.
[11] 李延忠. 肥胖与阻塞性睡眠呼吸暂停[J]. 山东大学耳鼻喉眼学报, 2016, 30(5): 1-4.
[12] 李兰根, 伟伟, 张玉凤, 格日乐图, 杨佳, 张艳梅. SIRT1抗视网膜色素上皮细胞氧化应激作用的实验研究[J]. 山东大学耳鼻喉眼学报, 2015, 29(6): 56-59.
[13] 李国俊1,2,潘新良3,雷大鹏3,陈兴明4,陈晓红5,宋西成6. 口咽部鳞状细胞癌与性行为和人乳头状瘤病毒感染[J]. 山东大学耳鼻喉眼学报, 2013, 27(1): 1-7.
[14] 毕宏生,李树杰,崔 彦,王 慧 . 茶多酚防治STZ诱导的大鼠糖尿病性白内障的机制[J]. 山东大学耳鼻喉眼学报, 2008, 22(1): 1-05 .
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!