瞬时受体电位信号通路在肝细胞癌中的表达及生物学功能

doi:10.3969/j.issn.1006-5725.2024.06.003

Abstract

Abstract:

In recent years， the morbidity and mortality of hepatocellular carcinoma （ HCC ） have been increasing worldwide， and the treatment strategies for HCC are still insufficient， which highlights the importance of exploring the pathogenesis and progression of HCC. Transient receptor potential （ TRP ） pathway is an important non-selective cation pathway， which is closely related to inflammatory response and sensory conduction. At present， a number of studies have shown that TRP pathway is also involved in the occurrence and development of HCC， inducing HCC invasion and migration. However， the overall potential mechanism and possible signal transduction pathways of TRP pathway in HCC remain unclear. Therefore， this article discusses the abnormal expression of TRP pathway in HCC， and reviews the key biological events of TRP pathway involved in the formation and progression of HCC， such as chronic liver inflammation-fibrosis progression， HCC cell proliferation， migration， apoptosis and HCC stem cell generation， and looks forward to its application prospect in HCC treatment. The aim is to better understand the significance of TRP pathway in HCC， help to find new therapeutic targets and effective drugs， and open up a new situation for future clinical treatment.

Key words: TRP pathway, hepatocellular carcinoma, expression characteristics, biological functions

CLC Number:

R735.7

Zhipeng WU,Yuqin ZHANG,Minggang WANG,Rongzhen ZHANG,Dewen. MAO. Expression and biological function of TRP signaling pathway in hepatocellular carcinoma[J]. The Journal of Practical Medicine, 2024, 40(6): 743-747.

Figures/Tables 1

References 30

1	SUNG H， FERLAY J， SIEGEL R L， 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 doi: 10.3322/caac.21660
2	VILLANUEVA A， HERNANDEZ-GEA V， LLOVET J M. Medical therapies for hepatocellular carcinoma： a critical view of the evidence［J］. Nat Rev Gastroenterol Hepatol， 2013，10（1）：34-42. doi:10.1038/nrgastro.2012.199 doi: 10.1038/nrgastro.2012.199
3	ANWANWAN D， SINGH S K， SINGH S， et al. Challenges in liver cancer and possible treatment approaches［J］. Biochim Biophys Acta Rev Cancer， 2020，1873（1）：188314. doi:10.1016/j.bbcan.2019.188314 doi: 10.1016/j.bbcan.2019.188314
4	COSENS D J， MANNING A. Abnormal electroretinogram from a Drosophila mutant［J］. Nature， 1969，224（5216）：285-287. doi:10.1038/224285a0 doi: 10.1038/224285a0
5	NILIUS B， OWSIANIK G. The transient receptor potential family of ion channels［J］. Genome Biol， 2011，12（3）：218. doi:10.1186/gb-2011-12-3-218 doi: 10.1186/gb-2011-12-3-218
6	SHAPOVALOV G， RITAINE A， SKRYMA R， et al. Role of TRP ion channels in cancer and tumorigenesis［J］. Semin Immunopathol， 2016，38（3）：357-369. doi:10.1007/s00281-015-0525-1 doi: 10.1007/s00281-015-0525-1
7	BOUSTANY C EL， BIDAUX G， ENFISSI A， et al. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation［J］. Hepatology， 2008，47（6）：2068-2077. doi:10.1002/hep.22263 doi: 10.1002/hep.22263
8	STOKLOSA P， BORGSTROM A， KAPPEL S， et al. TRP channels in digestive tract cancers［J］. Int J Mol Sci， 2020，21：1877. doi:10.3390/ijms21051877 doi: 10.3390/ijms21051877
9	MIAO X， LIU G， XU X， et al. High expression of vanilloid receptor-1 is associated with better prognosis of patients with hepatocellular carcinoma［J］. Cancer Genet Cytogenet， 2008，186（1）：25-32. doi:10.1016/j.cancergencyto.2008.05.011 doi: 10.1016/j.cancergencyto.2008.05.011
10	LIU G， XIE C， SUN F， et al. Clinical significance of transient receptor potential vanilloid 2 expression in human hepatocellular carcinoma［J］. Cancer Genet Cytogenet， 2010， 197（1）：54-59. doi:10.1016/j.cancergencyto.2009.08.007 doi: 10.1016/j.cancergencyto.2009.08.007
11	KOH H H， CHOI S， PARK C K， et al. Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection［J］. Cancer Genomics Proteomics， 2022，19（2）：259-269. doi:10.21873/cgp.20318 doi: 10.21873/cgp.20318
12	WANG W， LIU P， ZHANG Y， et al. Expression and functions of transient receptor potential channels in liver diseases［J］. Acta Pharm Sin B， 2023，13（2）：445-459. doi:10.1016/j.apsb.2022.09.005 doi: 10.1016/j.apsb.2022.09.005
13	XU J， YANG Y， XIE R， et al. The NCX1/TRPC6 Complex Mediates TGFβ-Driven Migration and Invasion of Human Hepatocellular Carcinoma Cells［J］. Cancer Res， 2018，78（10）：2564-2576． doi:10.1158/0008-5472.can-17-2061 doi: 10.1158/0008-5472.can-17-2061
14	ZHU S， YE H， XU X， et al. Involvement of TRPC7-AS1 Expression in Hepatitis B Virus-Related Hepatocellular Carcinoma［J］. J Oncol， 2021，2021：8114327. doi:10.1155/2021/8114327 doi: 10.1155/2021/8114327
15	FANG Y， LIU G， XIE C， et al. Pharmacological inhibition of TRPV4 channel suppresses malignant biological behavior of hepatocellular carcinoma via modulation of ERK signaling pathway［J］. Biomed Pharmacother， 2018，101：910-919. doi:10.1016/j.biopha.2018.03.014 doi: 10.1016/j.biopha.2018.03.014
16	ROEHLEN N， CROUCHET E， BAUMERT T F. Liver Fibrosis： Mechanistic Concepts and Therapeutic Perspectives［J］. Cells， 2020， 9（4）：875. doi:10.3390/cells9040875 doi: 10.3390/cells9040875
17	LIU Q， LEI X， CAO Z， et al. TRPM8 deficiency attenuates liver fibrosis through S100A9-HNF4α signaling［J］. Cell Biosci， 2022，12（1）：58. doi:10.1186/s13578-022-00789-4 doi: 10.1186/s13578-022-00789-4
18	SELLI C， ERAC Y， KOSOVA B， et al. Silencing of TRPC1 regulates store-operated calcium entry and proliferation in Huh7 hepatocellular carcinoma cells［J］. Biomed Pharmacother， 2015，71：194-200. doi:10.1016/j.biopha.2015.02.024 doi: 10.1016/j.biopha.2015.02.024
19	ANAND P， FILIPENKO P， HUAMAN J， et al. Selective Inhibition of Liver Cancer Cells Using Venom Peptide［J］. Mar Drugs， 2019，17（10）：587. doi:10.3390/md17100587 doi: 10.3390/md17100587
20	SELLI C， PEARCE D A， SIMS A H， et al. Differential expression of storeoperated calcium-and proliferation-related genes in hepatocellular carcinoma cells following TRPC1 ion channel silencing［J］. Mol Cell Biochem， 2016， 420（1/2）：129-140． doi:10.1007/s11010-016-2776-0 doi: 10.1007/s11010-016-2776-0
21	CHEN Y， YU Y， SUN S， et al. Bradykinin promotes migration and invasion of hepatocellular carcinoma cells through TRPM7 and MMP2［J］. Exp Cell Res， 2016， 349（1）：68-76. doi:10.1016/j.yexcr.2016.09.022 doi: 10.1016/j.yexcr.2016.09.022
22	HUANG S P， CHEN J C， WU C C， et al. Capsaicin-induced apoptosis in human hepatoma HepG2 cells［J］. Anticancer Res， 2009， 29（1）：165-174.
23	HAN L， DI C X， MAO A H， et al. Mechanism of Capsazepine inducing apoptosis of human hepatocellular carcinoma cell line HepG2［J］. Chin J Cancer Prev Trea， 2015，22（10）：764-769.
24	CHEN W T， LIN G B， LIN S H， et al. Static magnetic field enhances the anticancer efficacy of capsaicin on HepG2 cells via capsaicin receptor TRPV1［J］. PLoS One， 2018，13（1）：e0191078. doi:10.1371/journal.pone.0191078 doi: 10.1371/journal.pone.0191078
25	ZHANG N， BAI S H， ZHANG F H， et al. Molecular markers and mechanisms for stemness maintenance of liver cancer stem cells： a review［J］. Chin J Biotech， 2021， 37（8）： 2719-2736.
26	HU Z， CAO X， FANG Y， et al. Transient receptor potential vanilloid-type 2 targeting on stemness in liver cancer［J］. Biomed Pharmacother， 2018， 105：697-706. doi:10.1016/j.biopha.2018.06.029 doi: 10.1016/j.biopha.2018.06.029
27	HUANG A， YANG X R， CHUNG W Y， et al. Targeted therapy for hepatocellular carcinoma［J］. Signal Transduct Target Ther， 2020，5（1）：146. doi:10.1038/s41392-020-00264-x doi: 10.1038/s41392-020-00264-x
28	BORT A， SPÍNOLA E， RODRÍGUEZ-HENCHE N， et al. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation［J］. Oncotarget，2017，8（50）：87684-87698. doi:10.18632/oncotarget.21196 doi: 10.18632/oncotarget.21196
29	THOPPIL R J， ADAPALA R K， CAPPELLI H C， et al. TRPV4 channel activation selectively inhibits tumor endothelial cell proliferation［J］. Sci Rep， 2015，5：14257. doi:10.1038/srep14257 doi: 10.1038/srep14257
30	ADAPALA R K， THOPPIL R J， GHOSH K， et al. Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy［J］. Oncogene， 2016，35（3）：314-322. doi:10.1038/onc.2015.83 doi: 10.1038/onc.2015.83

TRP通路	检测技术	样本量	结果	参考文献
TRPC6	免疫组化	150例HCC组织样本/与正常肝组织相比	HCC组织中TRPC6蛋白上调	［13］
TRPC6	qPCR	20例HCC组织样本/与正常肝组织相比	HCC组织中TRPC6 mRNA表现出过度表达	［7］
TRPC7	高通量测序	3例Ⅳ期 HBV相关HCC组织样本/与正常肝组织相比	TRPC7在HCC组织中的表达高于癌旁肝组织	［14］
TRPV1	RT-PCR	6对的HCC组织样本/与非肿瘤组织相比	6例非肿瘤组织中TRPV1 mRNA表现出过度表达；但在6例的HCC组织中有4例TRPV1 mRNA显示下调	［9］
	原位杂交法	15例HCC组织样本/与正常邻近组织相比	TRPV1 mRNA在HCC组织和正常组织中过表达
	免疫组化	62例HCC组织样本+62例非肿瘤对照组织	在62例HCC组织样本中30例观察到TRPV1蛋白过表达
TRPV2	免疫组化	55例HCC组织样本	在55例HCC组织中发现16例TRPV2蛋白表达增加	［10］
TRPV2	RT-PCR	13对HCC患者的肿瘤组织与非肿瘤组织mRNA提取物	在8例肝硬化组织和7例中分化、5例高分化以及6例低分化HCC患者肿瘤组织中TRPV2 mRNA表达水平升高	［10］
TRPV4	免疫组化	45例不同组织病理学类型的HCC组织	19例低分化HCC组织中16例TRPV4检测到TRPV4蛋白高表达；但在26例高、中分化HCC组织中，仅有9例检测到TRPV4高表达	［15］
TRPV6	免疫组化	219例HCC组织样本	在219例HCC组织中发现82例TRPV6蛋白低表达，137例TRPV6蛋白高表达	［11］

[1]	Fazhu FEI,Jiajun LU,Shuai ZHANG,Hao LI,Bin REN. Clinical application progress of immunization and targeted therapy for Hepatocellular Carcinoma in special populations [J]. The Journal of Practical Medicine, 2024, 40(6): 738-742.
[2]	Yuxin CHENG,Liang LIU,Shiyu DONG,Shengchao LI,Meng ZHANG. Research advances in exosomal proteins， mRNA and non⁃coding RNA regulation of Hepatocellular Carcinoma [J]. The Journal of Practical Medicine, 2024, 40(6): 748-755.
[3]	Junhong XU,Hongbing YAO,Xueyao WANG,Wei GUO,Caijin LU,Jiaxing WU,Jianhui JIANG,Dongkang ZHAO. Clinical efficacy of FOLFOX⁃HAIC combined with lenvatinib and PD⁃1 inhibitor in the treatment of intermediate and advanced Hepatocellular Carcinoma [J]. The Journal of Practical Medicine, 2024, 40(6): 762-767.
[4]	Lu YAN,Tianwei SHI. Expression of nicastrin， N1ICD and hes1 proteins in normal and cancerous liver tissues of mice [J]. The Journal of Practical Medicine, 2024, 40(6): 768-772.
[5]	Yi WANG,Shuo HE,Siyun YANG,Jun. ZHANG. In vitro study of 5⁃FU combined with rhCYGB in treating hypoxia⁃induced chemotherapy resistance of hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2024, 40(22): 3146-3154.
[6]	Hua WANG,Yue HEI,Miao SUN,Yanchuang SUN,Juan HAN,Juanhua. SUN. Efficacy of bevacizumab combined with raltitrexed in the treatment of unresectable hepatocellular carcinoma and its influence on adverse reactions and survival rate [J]. The Journal of Practical Medicine, 2024, 40(21): 3061-3066.
[7]	WU Linghong, ZHOU Min, LU Yao, ZHU Guangwei.. Value of neutrophil/lymphocyte ratio and its variation value in predicting risk of acute liver function deteri⁃ oration after interventional treatment of hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(6): 713-719.
[8]	ZHAN Yi, NI Caifang, ZHONG Binyan, TIAN Pengcheng.. Research advances of ALBI grade for liver function assessment and prognosis stratification [J]. The Journal of Practical Medicine, 2023, 39(3): 381-385.
[9]	Yan LIU,Donghua ZHANG,Yuqian HUANG,Youshun LIU,Ji. HUANG. Inhibitory effect of pristimerin on diethylnitrosamine⁃induced hepatocellular carcinoma in rats by regulating ROS/ASK1/JNK signal pathway [J]. The Journal of Practical Medicine, 2023, 39(20): 2597-2602.
[10]	LI Feiyan , ZHANG Riyun, WANG Na, WANG Minggang, MAO Dewen. . The role of phospholipase A2 in the development of Hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(15): 1857-1861.
[11]	LIU Wenying, QUE Yuan, OUYANG Zaixing, ZHU Jianhua, WU Liming, TAN Yong, SONG Hao, ZHU Yuzhen, HUANG Congyun.. Clinical application value of terminal branches portal vein embolization and multimode imaging technolo⁃ gy in precise hepatectomy of huge hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2023, 39(12): 1546-1550.
[12]	WEN Jing, HE Rong, ZHANG Hongwei, XIONG Qiqiu, JIA Zhe, ZHANG Ke. . Evaluation of safety and efficacy of simultaneous surgery for portal hypertension with hepatocellular carci⁃ noma [J]. The Journal of Practical Medicine, 2023, 39(11): 1416-1421.
[13]	WANG Junjie, XU Long, YUAN Guosheng, XU Xiaoming, ZHOU Xiaoyuan, LUO Runqi.. Efficacy and safety of sintilimab in combination with lenvatinib therapy as second⁃line regimen for patients with unresectable hepatocellular carcinoma [J]. The Journal of Practical Medicine, 2022, 38(9): 1130-1135.
[14]	LEI Linhan, ZHENG Dijie, WU Chunchen, ZHEN Jian, XIE Huahua, HUA Hao, SUN Chengyi, YU Chao. . LincRNA00858 regulates miR ⁃3126⁃5p to affect proliferation，migration and invasion of hepatocellularcarcinoma [J]. The Journal of Practical Medicine, 2022, 38(4): 427-433.
[15]	WEI Xueyan, LIN Qiuling, QIU Moqin, CHEN Peiqin, ZHOU Zihan, LIU Yingchun, LIANG Wei⁃ kang, ZHANG Ruoxin, YU Hongping.. Association of genetic variants of super⁃fnhancer region with survival of HBV⁃related hepatocellular carci⁃ noma [J]. The Journal of Practical Medicine, 2022, 38(24): 3059-3064.

Expression and biological function of TRP signaling pathway in hepatocellular carcinoma

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 1

References 30

Related Articles 15

Recommended Articles

Metrics

Comments