AccScience Publishing / GPD / Volume 3 / Issue 2 / DOI: 10.36922/gpd.3062
Submit to GPD
Cite this article
30
Download
505
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW

TOPK: A noteworthy target for lung cancer treatment

Wenbo Liu1,2,3 ,  Feng Zhu1 ,  Qiuhong Duan1 ,  Yafang Li1,3 ,  Shuang Zhao1 ,  Juanjuan Xiao1* ,  Yijie Zhang2,3*
Show Less
1 Translational Medical Center, Huaihe Hospital, Henan University, Kaifeng, Henan, China
2 Department of Respiratory, School of Second Clinical Medicine, Henan University, Kaifeng, Henan, China
3 Department of Respiratory, Huaihe Hospital of Henan University, Kaifeng, Henan, China
GPD 2024, 3(2), 3062 https://doi.org/10.36922/gpd.3062
Submitted: 29 February 2024 | Accepted: 15 May 2024 | Published: 12 June 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

T-LAK cell-originated protein kinase (TOPK) is a serine/threonine protein kinase that is specifically expressed in actively proliferating cells, such as normal testicular germ cells, lymphocytes, and various tumor cells. It plays a key role in multiple biological processes, such as cell growth, metastasis, drug resistance, angiogenesis, and inflammation, and is a promising therapeutic target for tumors. Aberrant TOPK overexpression or activation has been observed in lung cancer and is related to lung cancer occurrence and development, clinical outcome, and poor prognosis. The inhibition of TOPK has demonstrated significant therapeutic potential for reducing tumor growth and can even be used in combination with chemotherapy or radiotherapy. Thus, targeting TOPK provides a promising avenue for the prevention and treatment of lung cancer. This article reviews the role of TOPK in the occurrence, development, and drug resistance of lung cancer; summarizes the main signaling pathways affected by TOPK in lung cancer; and analyzes its therapeutic value. The role and potential of TOPK in targeted therapy, chemotherapy, radiotherapy, and immunotherapy for lung cancer are also discussed. In addition, the latest progress in the use of TOPK inhibitors for lung cancer treatment is summarized, and their future clinical application is discussed. Overall, TOPK is a valuable target for the treatment of lung cancer, and further development of specific TOPK inhibitors is indispensable for the comprehensive treatment of lung cancer.

Keywords
TOPK
Lung cancer
Cancer treatment
Inhibitors
Target
Funding
This work was supported by the National Natural Science Foundation of China (Grant no. 82260528, 8190284), and the International Cooperation Projects of Henan Province (Grant no. 232102521030).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Ishikawa C, Senba M, Mori N. Mitotic kinase PBK/TOPK as a therapeutic target for adult Tcell leukemia/lymphoma. Int J Oncol. 2018;53(2):801-814. doi: 10.3892/ijo.2018.4427

 

  1. Gaudet S, Branton D, Lue RA. Characterization of PDZ-binding kinase, a mitotic kinase. Proc Natl Acad Sci U S A. 2000;97(10):5167-5172. doi: 10.1073/pnas.090102397

 

  1. Sun H, Zheng J, Xiao J, et al. TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC. Cell Death Dis. 2022;13(5):450. doi: 10.1038/s41419-022-04909-3

 

  1. Zykova TA, Zhu F, Wang L, et al. The T-LAK cell-originated protein kinase signal pathway promotes colorectal cancer metastasis. EBioMedicine. 2017;18:73-82. doi: 10.1016/j.ebiom.2017.04.003

 

  1. Li Y, Yang Z, Li W, et al. TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun. Oncotarget. 2016;7(6):6748-6764. doi: 10.18632/oncotarget.6826

 

  1. Xue P, Wang Y, Zeng F, et al. Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase. Oncotarget. 2017;8(16):27093-27104. doi: 10.18632/oncotarget.15636

 

  1. Zykova TA, Zhu F, Lu C, et al. Lymphokine-activated killer T-cell-originated protein kinase phosphorylation of histone H2AX prevents arsenite-induced apoptosis in RPMI7951 melanoma cells. Clin Cancer Res. 2006;12(23):6884-6893. doi: 10.1158/1078-0432.Ccr-06-0410

 

  1. Zykova TA, Zhu F, Vakorina TI, et al. T-LAK cell-originated protein kinase (TOPK) phosphorylation of Prx1 at Ser-32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through the regulation of Prx1 peroxidase activity. J Biol Chem. 2010;285(38):29138-29146. doi: 10.1074/jbc.M110.135905

 

  1. Lu H, Xiao J, Ke C, et al. TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell Death Dis. 2019;10(8):583. doi: 10.1038/s41419-019-1805-9

 

  1. Park JH, Yoon DS, Choi HJ, Hahm DH, Oh SM. Phosphorylation of IκBα at serine 32 by T-lymphokine-activated killer cell-originated protein kinase is essential for chemoresistance against doxorubicin in cervical cancer cells. J Biol Chem. 2013;288(5):3585-3593. doi: 10.1074/jbc.M112.422170

 

  1. Huang H, Lee MH, Liu K, Dong Z, Ryoo Z, Kim MO. PBK/ TOPK: An effective drug target with diverse therapeutic potential. Cancers (Basel). 2021;13(9):2232. doi: 10.3390/cancers13092232

 

  1. Zhang L, Wang F, Yi H, et al. The role of T-LAK cell-originated protein kinase in targeted cancer therapy. Mol Cell Biochem. 2022;477(3):759-769. doi: 10.1007/s11010-021-04329-5

 

  1. Kocarnik JM, Compton K, Dean FE, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 Cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study 2019. JAMA Oncol. 2022;8(3):420-444. doi: 10.1001/jamaoncol.2021.6987

 

  1. Raskova Kafkova L, Mierzwicka JM, Chakraborty P, et al. NSCLC: From tumorigenesis, immune checkpoint misuse to current and future targeted therapy. Front Immunol. 2024;15:1342086. doi: 10.3389/fimmu.2024.1342086

 

  1. Dougherty JD, Garcia AD, Nakano I, et al. PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase. J Neurosci. 2005;25(46):10773-10785. doi: 10.1523/jneurosci.3207-05.2005

 

  1. Zhu F, Zykova TA, Kang BS, et al. Bidirectional signals transduced by TOPK-ERK interaction increase tumorigenesis of HCT116 colorectal cancer cells. Gastroenterology. 2007;133(1):219-231. doi: 10.1053/j.gastro.2007.04.048

 

  1. Xiao J, Zhang L, Yi H, et al. Inhibiting ALK-TOPK signaling pathway promotes cell apoptosis of ALK-positive NSCLC. Cell Death Dis. 2022;13(9):828. doi: 10.1038/s41419-022-05260-3

 

  1. Park JH, Inoue H, Kato T, et al. TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer. Cancer Sci. 2017;108(3):488-496. doi: 10.1111/cas.13160

 

  1. Cai C, Yao S, Zou Y, et al. KRAS(G12C) mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer. J Cell Mol Med. 2023;27(12):1637-1652. doi: 10.1111/jcmm.17640

 

  1. Shih MC, Chen JY, Wu YC, et al. TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer. Oncogene. 2012;31(19):2389-2400. doi: 10.1038/onc.2011.419

 

  1. Park JH, Moon M, Kim JS, Oh SM. TOPK mediates hypoxia-induced epithelial-mesenchymal transition and the invasion of nonsmall-cell lung cancer cells via the HIF-1α/snail axis. Biochem Biophys Res Commun. 2021;534:941-949. doi: 10.1016/j.bbrc.2020.10.068

 

  1. Xiao J, Wang F, Lu H, et al. Targeting the COX2/MET/ TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells. Cell Death Dis. 2019;10(10):777. doi: 10.1038/s41419-019-2020-4

 

  1. Wei DC, Yeh YC, Hung JJ, et al. Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma. Cancer Sci. 2012;103(4):731-738. doi: 10.1111/j.1349-7006.2011.02197.x

 

  1. Lei B, Liu S, Qi W, et al. PBK/TOPK expression in non-small-cell lung cancer: Its correlation and prognostic significance with Ki67 and p53 expression. Histopathology. 2013;63(5):696-703. doi: 10.1111/his.12215

 

  1. Lei B, Qi W, Zhao Y, et al. PBK/TOPK expression correlates with mutant p53 and affects patients’ prognosis and cell proliferation and viability in lung adenocarcinoma. Hum Pathol. 2015;46(2):217-224. doi: 10.1016/j.humpath.2014.07.026

 

  1. Li J, Hou W. Expression patterns and clinical significances of PBK in lung cancer: An analysis based on Oncomine database. Transl Cancer Res. 2021;10(5):2036-2043. doi: 10.21037/tcr-20-3435

 

  1. Ma H, Zhang J, Shi Y, et al. PBK correlates with prognosis, immune escape and drug response in LUAD. Sci Rep. 2023;13(1):20452. doi:10.1038/s41598-023-47781-7

 

  1. Ramalingam SS, Owonikoko TK, Khuri FR. Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J Clin. 2011;61(2):91-112. doi: 10.3322/caac.20102

 

  1. Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021;27(8):1345-1356. doi: 10.1038/s41591-021-01450-2

 

  1. Matsuo Y, Park JH, Miyamoto T, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci Transl Med. 2014;6(259):259ra145. doi: 10.1126/scitranslmed.3010277

 

  1. Gao T, Hu Q, Hu X, et al. Novel selective TOPK inhibitor SKLB-C05 inhibits colorectal carcinoma growth and metastasis. Cancer Lett. 2019;445:11-23. doi: 10.1016/j.canlet.2018.12.016

 

  1. Zhao R, Huang H, Choi BY, et al. Cell growth inhibition by 3-deoxysappanchalcone is mediated by directly targeting the TOPK signaling pathway in colon cancer. Phytomedicine. 2019;61:152813. doi: 10.1016/j.phymed.2018.12.036

 

  1. Fu X, Zhao R, Yoon G, et al. 3-Deoxysappanchalcone inhibits skin cancer proliferation by regulating T-lymphokine-activated killer cell-originated protein kinase in vitro and in vivo. Front Cell Dev Biol. 2021;9:638174. doi: 10.3389/fcell.2021.638174

 

  1. Gao G, Zhang T, Wang Q, et al. ADA-07 suppresses solar ultraviolet-induced skin carcinogenesis by directly inhibiting TOPK. Mol Cancer Ther. 2017;16(9):1843-1854. doi: 10.1158/1535-7163.Mct-17-0212

 

  1. Zhao R, Choi BY, Wei L, et al. Acetylshikonin suppressed growth of colorectal tumour tissue and cells by inhibiting the intracellular kinase, T-lymphokine-activated killer cell-originated protein kinase. Br J Pharmacol. 2020;177(10):2303-2319. doi: 10.1111/bph.14981

 

  1. Zhang E, Yin S, Lu X, Ye L, Fan L, Hu H. Glycycoumarin sensitizes liver cancer cells to ABT-737 by targeting de novo lipogenesis and TOPK-survivin axis. Nutrients. 2018;10(3):353. doi: 10.3390/nu10030353

 

  1. Zeng X, Liu L, Zheng M, et al. Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2016;7(16):22460-22473. doi: 10.18632/oncotarget.7984

 

  1. Zheng M, Luan S, Gao S, et al. Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase. Oncotarget. 2017;8(24):39143-39153. doi: 10.18632/oncotarget.16609

 

  1. Vishchuk OS, Sun H, Wang Z, et al. PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth. Oncotarget. 2016;7(14):18763-18773. doi: 10.18632/oncotarget.7708

 

  1. Diao X, Yang D, Chen Y, Liu W. Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase. Biosci Rep. 2019;39(4):BSR20181692. doi: 10.1042/bsr20181692

 

  1. Fan X, Duan Q, Ke C, et al. Cefradine blocks solar-ultraviolet induced skin inflammation through direct inhibition of T-LAK cell-originated protein kinase. Oncotarget. 2016;7(17):24633-24645. doi: 10.18632/oncotarget.8260

 

  1. Zou L, Gao Z, Zeng F, et al. Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase. Oncol Lett. 2019;18(4):3517-3526. doi: 10.3892/ol.2019.10721

 

  1. Kang NJ, Lee KW, Kim BH, et al. Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis. 2011;32(6):921-928. doi: 10.1093/carcin/bgr022

 

  1. Yang J, Yuan D, Xing T, et al. Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase. J Ginseng Res. 2016;40(4):400-408. doi: 10.1016/j.jgr.2016.03.007

 

  1. Huang H, Mu X, Deng J, Xiao S, Luo Z, Chen G. Solvation free energy for selection of an aqueous two-phase system: Case in paeonol extraction from cortex moutan. ACS Omega. 2022;7(35):30920-30929. doi: 10.1021/acsomega.2c02693

 

  1. Zhao S, Cui J, Cao L, et al. Xanthohumol inhibits non-small cell lung cancer via directly targeting T-lymphokine-activated killer cell-originated protein kinase. Phytother Res. 2023;37(7):3057-3068. doi: 10.1002/ptr.7799

 

  1. Lu S, Ye L, Yin S, et al. Glycyrol exerts potent therapeutic effect on lung cancer via directly inactivating T-LAK cell-originated protein kinase. Pharmacol Res. 2019;147:104366.

 

  1. Lu H, Huang Y, Ni X, et al. TOPK promotes the development of psoriasis and worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity. J Eur Acad Dermatol Venereol. 2023;38:851-63. doi: 10.1111/jdv.19724

 

  1. Majeed U, Manochakian R, Zhao Y, Lou Y. Targeted therapy in advanced non-small cell lung cancer: Current advances and future trends. J Hematol Oncol. 2021;14(1):108. doi: 10.1186/s13045-021-01121-2

 

  1. Tsao AS, Scagliotti GV, Bunn PA Jr., et al. Scientific advances in lung cancer 2015. J Thorac Oncol. 2016;11(5):613-638. doi: 10.1016/j.jtho.2016.03.012

 

  1. Cheng Y, Zhang T, Xu Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. MedComm (2020). 2021;2(4):692-729. doi: 10.1002/mco2.105

 

  1. Wang P, Li T, Fang L, Chen D, Qi H, Gu C. UPF1 regulates FOXO1 protein expression by promoting PBK transcription in non-small cell lung cancer. Biochem Biophys Res Commun. 2023;666:10-20. doi: 10.1016/j.bbrc.2023.05.001

 

  1. Park JH, Park SA, Lee YJ, Park HW, Oh SM. PBK attenuates paclitaxel-induced autophagic cell death by suppressing p53 in H460 non-small-cell lung cancer cells. FEBS Open Bio. 2020;10(5):937-950. doi: 10.1002/2211-5463.12855

 

  1. Juloori A, Vokes EE. Beyond PACIFIC: Uncharted waters. J Thorac Oncol. 2021;16(5):715-718. doi: 10.1016/j.jtho.2021.02.006

 

  1. Tan B, Zhang J, Wang W, Ma H, Yang Y. Tumor-suppressive E3 ubiquitin ligase CHIP inhibits the PBK/ERK axis to repress stem cell properties and radioresistance in non-small cell lung cancer. Apoptosis. 2023;28(3-4):397-413. doi: 10.1007/s10495-022-01789-y

 

  1. Herbert KJ, Puliyadi R, Prevo R, et al. Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress. Cell Death Differ. 2021;28(4):1333-1346. doi: 10.1038/s41418-020-00655-1

 

  1. Sanmamed MF, Chen L. A Paradigm shift in cancer immunotherapy: From enhancement to normalization. Cell. 2018;175(2):313-326. doi: 10.1016/j.cell.2018.09.035

 

  1. Liu M, Yu X, Qu C, Xu S. Predictive value of gene databases in discovering new biomarkers and new therapeutic targets in lung cancer. Medicina (Kaunas). 2023;59(3):547. doi: 10.3390/medicina59030547

 

  1. Li J, Sun H, Fu M, et al. TOPK mediates immune evasion of renal cell carcinoma via upregulating the expression of PD-L1. iScience. 2023;26(7):107185. doi: 10.1016/j.isci.2023.107185

 

  1. Zhou B, Zang R, Zhang M, et al. Identifying novel tumor-related antigens and immune phenotypes for developing mRNA vaccines in lung adenocarcinoma. Int Immunopharmacol. 2022;109:108816. doi: 10.1016/j.intimp.2022.108816

 

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. doi: 10.3322/caac.21708

 

  1. Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018;29(Suppl 1):i10-i19. doi: 10.1093/annonc/mdx703

 

  1. Attwood MM, Fabbro D, Sokolov AV, Knapp S, Schiöth HB. Trends in kinase drug discovery: Targets, indications and inhibitor design. Nat Rev Drug Discov. 2021;20(11):839-861. doi: 10.1038/s41573-021-00252-y

 

  1. Oprea TI, Bologa CG, Brunak S, et al. Unexplored therapeutic opportunities in the human genome. Nat Rev Drug Discov. 2018;17(5):317-332. doi: 10.1038/nrd.2018.14

 

  1. Yang P, Meng M, Zhou Q. Oncogenic cancer/testis antigens are a hallmarker of cancer and a sensible target for cancer immunotherapy. Biochim Biophys Acta Rev Cancer. 2021;1876(1):188558. doi: 10.1016/j.bbcan.2021.188558
Share
Back to top
Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept