Research Progress of Carcinogenic Factors Related to HPV Infection Based on Ion Channels

doi:10.3870/j.issn.1672-0741.25.08.019

Abstract

Abstract: Ion channels are responsible for the flow of ions across cell membranes and play vital roles in human physiology,including the regulation of ion homeostasis,electrical excitability,and cell signaling.However,when ion channel function or expression is altered,these channels can interact with carcinogens,increasing susceptibility to HPV infection and inducing cancer.Therefore,this study focuses on potassium,sodium,and chloride ion channels,identifies HPV-related carcinogenic factors,elucidates relevant mechanisms and the potential for targeting ion channels for treatment,and provides a new approach to the clinical determination of HPV-related cancer early diagnosis,prognosis,and treatment.

Key words: HPV, ion channel, carcinogenic factor, molecular marker, targeted therapy

CLC Number:

R730.2

Liang Mingge, Ai Wenxia, Qi Ding et al. Research Progress of Carcinogenic Factors Related to HPV Infection Based on Ion Channels[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 423-430.

References

[1] Scott-Wittenborn N,Fakhry C.Epidemiology of HPV related malignancies[J].Semin Radiat Oncol,2021,31(4):286-296.
[2] Hochmann J,Parietti F,Martinez J,et al.Human papillomavirus type 18E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state[J].Mem Inst Oswaldo Cruz,2020,115:e190405.
[3] Graham S V.The human papillomavirus replication cycle,and its links to cancer progression:A comprehensive review[J].Clin Sci(Lond),2017,131(17):2201-2221.
[4] Bharadwaj A,Kempster E,Waisman D M.The annexin A2/S100A10 complex:the mutualistic symbiosis of two distinct proteins[J].Biomolecules,2021,11(12):1849.
[5] Seo J S,Svenningsson P.Modulation of ion channels and receptors by p11(S100A10)[J].Trends Pharmacol Sci,2020,41(7):487-497.
[6] Stewart J M.TRPV6 as a target for cancer therapy[J].J Cancer,2020,11(2):374-387.
[7] Wu X,Wang S,Li M,et al.Conditional reprogramming:next generation cell culture[J].Acta Pharm Sin B,2020,10(8):1360-1381.
[8] Huang J,Liu J,Qiu L.Transient receptor potential vanilloid 1 promotes EGFR ubiquitination and modulates EGFR/MAPK signalling in pancreatic cancer cells[J].Cell Biochem Funct,2020,38(4):401-408.
[9] Rubio K,Romero-Olmedo A J,Sarvari P,et al.Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer[J].Theranostics,2023,13(8):2384-2407.
[10] Wang J C K,Baddock H T,Mafi A,et al.Structure of the p53 degradation complex from HPV16[J].Nat Commun,2024,15(1):1842.
[11] He S,Moutaoufik M T,Islam S,et al.HERG channel and cancer:A mechanistic review of carcinogenic processes and therapeutic potential[J].Biochim Biophys Acta Rev Cancer,2020,1873(2):188355.
[12] Tomita T,Huibregtse J M,Matouschek A.A masked initiation region in retinoblastoma protein regulates its proteasomal degradation[J].Nat Commun,2020,11(1):2019.
[13] Qu X,Hamidi H,Johnson R M,et al.Ligand-activated EGFR/MAPK signaling but not PI3K,are key resistance mechanisms to EGFR-therapy in colorectal cancer[J].Nat Commun,2025,16(1):4332.
[14] Abdelaziz R,Tomczak A P,Neef A,et al.Revealing a hidden conducting state by manipulating the intracellular domains in K(v)10.1 exposes the coupling between two gating mechanisms[J].Elife,2024,12:RP91420.
[15] Diaz L,Bernadez-Vallejo S V,Vargas-Castro R,et al.The ph-ytochemical alpha-mangostin inhibits cervical cancer cell proliferation and tumor growth by downregulating E6/E7-HPV oncogenes and KCNH1 gene expression[J].Int J Mol Sci,2023,24(3):3055.
[16] Garcia-Ferreiro R E,Kerschensteiner D,Major F,et al.Mechanism of block of hEag1 K⁺ channels by imipramine and astemizole[J].J Gen Physiol,2004,124(4):301-317.
[17] Wang H,Yang X,Guo Y,et al.HERG1 promotes esophageal squamous cell carcinoma growth and metastasis through TXNDC5 by activating the PI3K/Akt pathway[J].J Exp Clin Cancer Res,2019,38(1):324.
[18] Liu L,Chen Y,Zhang Q,et al.Silencing of KCNA1 suppresses the cervical cancer development via mitochondria damage[J].Channels(Austin),2019,13(1):321-330.
[19] Xu H,Miao J,Liu S,et al.Long non-coding RNA KCNQ1 overlapping transcript 1 promotes the progression of esophageal squamous cell carcinoma by adsorbing microRNA-133b[J].Clinics(Sao Paulo),2021,76(4):e2175.
[20] Ramirez A,Vera E,Gamboa-Dominguez A,et al.Calcium-activated potassium channels as potential early markers of human cervical cancer[J].Oncol Lett,2018,15(5):7249-7254.
[21] Glaser F,Hundehege P,Bulk E,et al.K(Ca)channel blockers increase effectiveness of the EGF receptor TK inhibitor erlotinib in non-small cell lung cancer cells(A549)[J].Sci Rep,2021,11(1):18330.
[22] Vazquez-Sanchez A Y,Hinojosa L M,Parraguirre-Martinez S,et al.Expression of K(ATP)channels in human cervical cancer:Potential tools for diagnosis and therapy[J].Oncol Lett,2018,15(5):6302-6308.
[23] Kamuene J M,Xu Y,Plant L D.The pharmacology of two-pore domain potassium channels[J].Handb Exp Pharmacol,2021,267(267):417-443.
[24] Lopez-Charcas O,Pukkanasut P,Velu S E,et al.Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers[J].iScience,2021,24(4):102270.
[25] Lopez-Charcas O,Espinosa A M,Alfaro A,et al.The invasiveness of human cervical cancer associated to the function of Na(V)1.6 channels is mediated by MMP-2 activity[J].Sci Rep,2018,8(1):12995.
[26] Ariyoshi W,Okinaga T,Chaweewannakorn W,et al.Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33[J].J Cell Physiol,2017,232(12):3481-3495.
[27] Wang X,Xiao Y,Huang M,et al.Effect of TRPM2-mediated calcium signaling on cell proliferation and apoptosis in esophageal squamous cell carcinoma[J].Technol Cancer Res Treat,2021,20:15330338211045213.
[28] Liu C,Zhu L L,Xu S G,et al.ENaC/DEG in tumor development and progression[J].J Cancer,2016,7(13):1888-1891.
[29] Yang Y,Zhong X,Lan Y,et al.Aberrant inactivation of SCNN1 G promotes the motility of head and neck squamous cell carcinoma[J].Pathol Res Pract,2022,240:154175.
[30] Guan Y,Luan Y,Xie Y,et al.Chloride channel-3 is required for efficient tumour cell migration and invasion in human cervical squamous cell carcinoma[J].Gynecol Oncol,2019,153(3):661-669.
[31] Katsurahara K,Shiozaki A,Kosuga T,et al.ANO9 regulated cell cycle in human esophageal squamous cell carcinoma[J].Ann Surg Oncol,2020,27(9):3218-3230.
[32] Vyas A,Gomez-Casal R,Cruz-Rangel S,et al.Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy[J].Proc Natl Acad Sci USA,2022,119(12):e2100670119.
[33] Yoshimoto S,Matsuda M,Kato K,et al.Volume-regulated ch-loride channel regulates cell proliferation and is involved in the possible interaction between TMEM16A and LRRC8 A in human metastatic oral squamous cell carcinoma cells[J].Eur J Pharmacol,2021,895:173881.
[34] Shi S,Ma B,Sun F,et al.Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell viability[J].J Biol Chem,2021,297(3):101016.
[35] Chen L,Konig B,Liu T,et al.More than just a pressure relief valve:physiological roles of volume-regulated LRRC8 anion channels[J].Biol Chem,2019,400(11):1481-1496.
[36] Siemer S,Fauth T,Scholz P,et al.Profiling cisplatin resistance in head and neck cancer:A critical role of the VRAC ion channel for chemoresistance[J].Cancers(Basel),2021,13(19):4831.
[37] Huang J J,Lin J,Chen X,et al.Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis[J].Medicine(Baltimore),2021,100(45):e27739.
[38] Edwards J C,Kahl C R.Chloride channels of intracellular membranes[J].FEBS Lett,2010,584(10):2102-2111.
[39] Yasuda Y,Nagano T,Jimbo N,et al.Chloride intracellular channel 1 expression is associated with poor prognosis of lung adenocarcinoma[J].Anticancer Res,2022,42(1):271-277.
[40] Suh K S,Crutchley J M,Koochek A,et al.Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers[J].Clin Cancer Res,2007,13(1):121-131.
[41] De Guadalupe Chavez-Lopez M,Hernandez-Gallegos E,Va-zquez-Sanchez A Y,et al.Antiproliferative and proapoptotic effects of astemizole on cervical cancer cells[J].Int J Gynecol Cancer,2014,24(5):824-828.
[42] Garcia-Quiroz J,Camacho J.Astemizole:an old anti-histamine as a new promising anti-cancer drug[J].Anticancer Agents Med Chem,2011,11(3):307-314.
[43] Pillozzi S,D’amico M,Bartoli G,et al.The combined activation of K(Ca)3.1 and inhibition of K(v)11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells[J].Br J Cancer,2018,118(2):200-212.
[44] Fuchs E,Messerer D A C,Karpel-Massler G,et al.Block of voltage-gated sodium channels as a potential novel anti-cancer mechanism of TIC10[J].Front Pharmacol,2021,12:737637.
[45] Lee A,Fraser S P,Djamgoz M B A.Propranolol inhibits neonatal Nav1.5 activity and invasiveness of MDA-MB-231 breast cancer cells:Effects of combination with ranolazine[J].J Cell Physiol,2019,234(12):23066-23081.
[46] Guo S,Chen Y,Pang C,et al.Matrine is a novel inhibitor of the TMEM16A chloride channel with antilung adenocarcinoma effects[J].J Cell Physiol,2019,234(6):8698-8708.
[47] 杜锐,张莹莹,户庆峰.苦参碱注射液对宫颈癌患者化疗增敏作用和生存质量、免疫功能的影响[J].中华中医药学刊,2018,36(12):3051-3055.
Du R,Zhang Y Y,Hu Q F.Effects of matrine injection on chemosensitivity,quality of life,and immune function in cervical cancer patients[J].Chinese Archives of Traditional Chinese Medicine,2018,36(12):3051-3055.
[48] Fan J J,Huang X.Ion channels in cancer:Orchestrators of electrical signaling and cellular crosstalk[J].Rev Physiol Biochem Pharmacol,2022,183(8):103-133.