Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2021, Vol. 35 ›› Issue (1): 119-124.doi: 10.6040/j.issn.1673-3770.0.2020.089

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Research progress on differentially-expressed protein kinases and inhibitors in hypopharyngeal carcinoma

WANG Yayue1,2Overview,SUN Juan2Guidance   

  1. 1. Graduate School of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China;
    2. Department of Otolaryngology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China
  • Published:2021-02-01

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Abstract: Among tumors of the head and neck, hypopharyngeal cancer is highly malignant and patients suffering from it have a poor quality of life, usually with a poor prognosis. Surgery is the main method of treatment of hypopharyngeal cancer, assisted by radiotherapy and chemotherapy. After surgery, the patient's laryngeal function is seriously impaired. Finding a treatment method that can protect the laryngeal function as much as possible is the focus of current research. Targeted therapy is of great significance to protecting the laryngeal function and improving the quality of life of patients with hypopharyngeal carcinoma. The study found that a variety of protein-kinase-mediated signaling pathways and genes are involved in the development of this pathology. Now, protein kinases PKC-β, CDK4/6, Cdc42, Rac1, and STK33, which might have an important role in this process, CK2 and PHLPP are reviewed. There is hope that protein kinase inhibitors would provide new directions for the treatment of hypopharyngeal cancer.

Key words: Hypopharyngeal carcinoma, Tumor, Protein kinase, Protein kinase inhibitor, Target

CLC Number: 

  • R739
[1] 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. doi:10.6040/j.issn.1673-3770.0.2018.058. WU Jing, LIU Yehai. Targeted therapy for head and neck squamous cell carcinoma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(5): 97-102. doi:10.6040/j.issn.1673-3770.0.2018.058.
[2] Vengaloor Thomas T, Nittala MR, Bhanat E, et al. Management of advanced-stage hypopharyngeal carcinoma: 25-year experience from a tertiary care medical center[J]. Cureus, 2020, 12(1): e6679. doi:10.7759/cureus.6679.
[3] 周梁. 下咽癌的治疗进展[J]. 中国耳鼻咽喉颅底外科杂志, 2019, 25(4): 333-338. doi:10.11798/j.issn.1007-1520.201904001. ZHOU Liang. Progress on treatment of hypopharyngeal carcinoma[J]. Chinese Journal of Otorhinolaryngology-Skull Base Surgery, 2019, 25(4): 333-338. doi:10.11798/j.issn.1007-1520.201904001.
[4] 崔晓波. 诱导化疗在局部晚期下咽癌治疗中的意义[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 10-17. doi:10.6040/j.issn.1673-3770.1.2019.027. CUI Xiaobo. Significance of induction chemotherapy in late treatment of locally advanced hypo-pharyngeal cancer[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 10-17. doi:10.6040/j.issn.1673-3770.1.2019.027.
[5] Bhullar KS, Lagarón NO, McGowan EM, et al. Kinase-targeted cancer therapies: progress, challenges and future directions[J]. Mol Cancer, 2018, 17: 48. doi:10.1186/s12943-018-0804-2.
[6] Ardito F, Giuliani M, Perrone D, et al. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy(Review)[J]. Int J Mol Med, 2017, 40(2): 271-280. doi:10.3892/ijmm.2017.3036.
[7] Cheng HJ, Wang WW, Wang GK, et al. Silencing ras-related C3 botulinum toxin substrate 1 inhibits growth and migration of hypopharyngeal squamous cell carcinoma via the P38 mitogen-activated protein kinase signaling pathway[J]. Med Sci Monit, 2018, 24: 768-781. doi:10.12659/msm.907468.
[8] Huang LY, Chen C, Zhang GD, et al. STK33 overexpression in hypopharyngeal squamous cell carcinoma: possible role in tumorigenesis[J]. BMC Cancer, 2015, 15: 13. doi:10.1186/s12885-015-1009-3.
[9] Lian HW, Su M, Zhu YJ, et al. Protein kinase CK2, a potential therapeutic target in carcinoma management[J]. Asian Pac J Cancer Prev, 2019, 20(1): 23-32. doi:10.31557/apjcp.2019.20.1.23.
[10] Newton AC. Protein kinase C: perfectly balanced[J]. Crit Rev Biochem Mol Biol, 2018, 53(2): 208-230. doi:10.1080/10409238.2018.1442408.
[11] 黄来全, 刘大翔. BTK与PKCβ在多发性骨髓瘤中表达及调控的信号通路机制研究[J]. 东南大学学报(医学版), 2018, 37(4): 578-583. doi:10.3969/j.issn.1671-6264.2018.04.005. HUANG Laiquan, LIU Daxiang. Expression of BTK and PKCβin multiple myeloma and the mechanism of its regulated signaling pathway[J]. Journal of Southeast University(Medical Science Edition), 2018, 37(4): 578-583. doi:10.3969/j.issn.1671-6264.2018.04.005.
[12] Zhu J, He YZ, Li J, et al. Combination of enzastaurin and ibrutinib synergistically induces anti-tumor effects in diffuse large B cell lymphoma[J]. Blood, 2018, 132(Supplement 1): 1666. doi:10.1182/blood-2018-99-110571.
[13] 李冠军, 董桂青, 李宇玥, 等. 抗肿瘤新药Enzastaurin的药理学及其临床研究进展[J]. 中国药房, 2011, 22(38): 3613-3616.
[14] Tarrado-Castellarnau M, de Atauri P, Tarragó-Celada J, et al. De novo MYC addiction as an adaptive response of cancer cells to CDK 4/6 inhibition[J]. Mol Syst Biol, 2017, 13(10): 940. doi:10.15252/msb.20167321.
[15] Goel S, DeCristo MJ, McAllister SS, et al. CDK4/6 inhibition in cancer: beyond cell cycle arrest[J]. Trends Cell Biol, 2018, 28(11): 911-925. doi:10.1016/j.tcb.2018.07.002.
[16] 付彬, 莫春梅, 覃艳春, 等. CDK4/6抑制剂治疗恶性肿瘤研究进展[J]. 海南医学院学报, 2019, 25(21): 1676-1680. doi:10.13210/j.cnki.jhmu.20191030.001. FU Bin, MO Chunmei, QIN Yanchun, et al. Progress of CDK4/6 inhibitors in treatment of malignant tumors[J]. Journal of Hainan Medical University, 2019, 25(21): 1676-1680. doi:10.13210/j.cnki.jhmu.20191030.001.
[17] Klein ME, Kovatcheva M, Davis LE, et al. CDK4/6 inhibitors: the mechanism of action may not be as simple as once thought[J]. Cancer Cell, 2018, 34(1): 9-20. doi:10.1016/j.ccell.2018.03.023.
[18] Peurois F, Veyron S, Ferrandez Y, et al. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering[J]. Biochem J, 2017, 474(7): 1259-1272. doi:10.1042/bcj20170015.
[19] Møller LLV, Klip A, Sylow L. Rho GTPases-emerging regulators of glucose homeostasis and metabolic health[J]. Cells, 2019, 8(5): 434. doi:10.3390/cells8050434.
[20] Maldonado MDM, Dharmawardhane S. Targeting rac and Cdc42 GTPases in cancer[J]. Cancer Res, 2018. doi:10.1158/0008-5472.can-18-0619.
[21] 李楠静, 刘明, 张又, 等. Rho GTP酶与肿瘤细胞耐药性的关系研究进展[J]. 山东医药, 2018, 57(7): 99-101. doi:10.3969/j.issn.1002-266X.2018.07.031.
[22] 郑艳秋, 胡文良, 崔晓波, 等. CDC42抑制剂ML141对喉癌Hep-2细胞增殖的抑制作用[J]. 现代生物医学进展, 2016, 16(4): 644-646, 651. doi:10.13241/j.cnki.pmb.2016.04.010. ZHENG Yanqiu, HU Wenliang, CUI Xiaobo, et al. CDC42 inhibitor ML141 suppresses laryngeal cancer hep-2 cell proliferation[J]. Progress in Modern Biomedicine, 2016, 16(4): 644-646, 651. doi:10.13241/j.cnki.pmb.2016.04.010.
[23] Chen C, Huang LY, Zhang GD, et al. STK33 potentiates the malignancy of hypopharyngeal squamous carcinoma: Possible relation to calcium[J]. Cancer Biol Ther, 2016, 17(9): 976-984. doi:10.1080/15384047.2016.1210739.
[24] Chua M, Ortega C, Sheikh A, et al. CK2 in cancer: cellular and biochemical mechanisms and potential therapeutic target[J]. Pharmaceuticals, 2017, 10(4): 18. doi:10.3390/ph10010018.
[25] Zhang F, Yang B, Shi SL, et al. RNA interference(RNAi)mediated stable knockdown of protein casein kinase 2-alpha(CK2α)inhibits migration and invasion and enhances cisplatin-induced apoptosis in HEp-2 laryngeal carcinoma cells[J]. Acta Histochem, 2014, 116(6): 1000-1006. doi:10.1016/j.acthis.2014.04.001.
[26] Ortega CE, Seidner Y, Dominguez I. Mining CK2 in cancer[J]. PLoS One, 2014, 9(12): e115609. doi:10.1371/journal.pone.0115609.
[27] Grzechnik AT, Newton AC. PHLPPing through history: a decade in the life of PHLPP phosphatases[J]. Biochem Soc Trans, 2016, 44(6): 1675-1682. doi:10.1042/bst20160170.
[28] Qiu YH, Li XY, Yi B, et al. Protein phosphatase PHLPP induces cell apoptosis and exerts anticancer activity by inhibiting Survivin phosphorylation and nuclear export in gallbladder cancer[J]. Oncotarget, 2015, 6(22): 19148-19162. doi:10.18632/oncotarget.3721.
[29] Zhou JY, Yu XM, Wang J, et al. Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma[J]. PLoS One, 2015, 10(3): e0119405. doi:10.1371/journal.pone.0119405.
[30] Gao TY, Furnari F, Newton AC. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth[J]. Mol Cell, 2005, 18(1): 13-24. doi:10.1016/j.molcel.2005.03.008.
[31] Qiao M, Wang YQ, Xu XE, et al. Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis[J]. Mol Cell, 2010, 38(4): 512-523. doi:10.1016/j.molcel.2010.03.017.
[32] 胡文良, 郑艳秋, 崔晓波, 等. 下咽癌中差异表达的蛋白激酶及其抑制剂的生物信息学筛选[J]. 山东大学耳鼻喉眼学报, 2016, 30(3): 24-28, 36. doi: 10.6040/j.issn.1673-3770.0.2015.340. HU Wenliang, ZHENG Yanqiu, CUI Xiaobo, et al. Bioinformatic screening of differentially expressed protein kinases and their inhibitors in hypopharyngeal cancer[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2016, 30(3): 24-28, 36. doi: 10.6040/j.issn.1673-3770.0.2015.340.
[33] Marei H, Malliri A. Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms[J]. Small Gtpases, 2017, 8(3): 139-163. doi:10.1080/21541248.2016.1211398.
[34] Michaelis M, Rothweiler F, Löschmann N, et al. Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status[J]. Oncotarget, 2015, 6(19): 17605-17620. doi:10.18632/oncotarget.2889.
[35] Spring LM, Zangardi ML, Moy B, et al. Clinical management of potential toxicities and drug interactions related to cyclin-dependent kinase 4/6 inhibitors in breast cancer: practical considerations and recommendations[J]. Oncol, 2017, 22(9): 1039-1048. doi:10.1634/theoncologist.2017-0142.
[36] Ku BM, Yi SY, Koh J, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma[J]. Oncotarget, 2016, 7(12): 14803-14813. doi:10.18632/oncotarget.7543.
[37] 徐永茹, 徐平, 徐锋, 等. CDC42与癌症[J]. 军事医学, 2016, 40(3): 256-260. doi:10.7644/j.issn.1674-9960.2016.03.023. XU Yongru, XU Ping, XU Feng, et al. The role of CDC42 in cancer[J]. Military Medical Sciences, 2016, 40(3): 256-260. doi:10.7644/j.issn.1674-9960.2016.03.023.
[38] Schnitzler A, Gratz A, Bollacke A, et al. A π-halogen bond of dibenzofuranones with the gatekeeper Phe113 in human protein kinase CK2 leads to potent tight binding inhibitors[J]. Pharmaceuticals, 2018, 11(1): 23. doi:10.3390/ph11010023.
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