连接蛋白26在肿瘤中的研究进展

doi:10.11904/j.issn.1002-3070.2022.02.011

摘要/Abstract

摘要： 近年来,研究证明连接蛋白形成的间隙连接(Gap junction,GJ)在介导肿瘤细胞间通讯起到不可忽视的作用。而异常的连接蛋白26(Connexin 26,Cx26)表达也被证实与肿瘤的发生进展和不良预后相关,因此对Cx26进行生物标记物分析以及深入研究如何介导不同癌症表型,有利于开发临床上基于Cx26的可行诊断和治疗方法。在这篇综述中,我们对不同癌症中Cx26的表达和功能进行了概述,并进一步讨论当前临床上利用Cx26进行肿瘤早期诊断和治疗的可能性。

关键词: 连接蛋白26, 间隙连接, 癌症, 癌症治疗, 治疗抵抗

Abstract: In recent years,studies have shown that gap junctions(GJ)formed by connexin play a non-negligible role in mediating communication between tumor cells.The abnormal expression of connexin 26(Cx26)has also been confirmed to be associated with tumor occurrence,progression and poor prognosis.Therefore,biomarker analysis of Cx26 and in-depth study of how it mediates different cancer phenotypes are beneficial to the development of clinical on feasible Cx26-based diagnostic and therapeutic approaches.In this review,we provide an overview of the expression and function of Cx26 in different cancers,and will further discuss the current clinical possibilities of using Cx26 for early tumor diagnosis and treatment.

Key words: Connexin 26, Gap junction, Cancer, Cancer therapy, Therapy resistance.

中图分类号:

陈德嘉, 娄阁. 连接蛋白26在肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2022, 36(2): 162-166.

CHEN Dejia, LOU Ge. Research progress of Connexin26 in tumors[J]. Journal of Practical Oncology, 2022, 36(2): 162-166.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2022/V36/I2/162

参考文献

1 Global Burden of Disease Cancer Collaboration,Fitzmaurice C,Allen C,et al.Global,regional,and national cancer incidence,mortality,years of life lost,years lived with disability,and disability-adjusted life-years for 32 cancer groups,1990 to 2015:a systematic analysis for the global burden of disease study[J].JAMA Oncol,2017,3(4):524-548.
2 Welch HG,Kramer BS,Black WC,et al.Epidemiologic signatures in cancer[J].N Engl J Med,2019,381(14):1378-1386.
3 Aasen T,Mesnil M,Naus CC,et al.Gap junctions and cancer:communicating for 50 years[J].Nat Rev Cancer,2016,16(12):775-788.
4 Aasen T,Leithe E,Graham SV,et al.Connexins in cancer:bridging the gap to the clinic[J].Oncogene,2019,38(23):4429-4451.
5 Oshima A.Structure and closure of connexin gap junction channels[J].FEBS Lett,2014,588(8):1230-1237.
6 Nalewajska M,Marchelek-My＇sliwiec M,Opara-Bajerowicz M,et al.Connexins-therapeutic targets in cancers[J].Int J Mol Sci,2020,21(23):9119-9143.
7 Maeda S,Nakagawa S,Suga M,et al.Structure of the connexin 26 gap junction channel at 3.5 A resolution[J].Nature,2009,458(7238):597-602.
8 Sinyuk M,Mulkearns-Hubert E,Reizes O,et al.Cancer connectors:connexins,gap junctions,and communication[J].Front Oncol,2018:646-663.
9 Saez JC,Berthoud VM,Branes MC,et al.Plasma membrane channels formed by connexins:their regulation and functions[J].Physiol Rev,2003,83(4):1359-1400.
10 Ramadan R,Baatout S,Aerts A,et al.The role of connexin proteins and their channels in radiation-induced atherosclerosis[J].Cell Mol Life Sci,2021,78(7):3087-3103.
11 Naoi Y,Miyoshi Y,Taguchi T,et al.Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer[J].Breast Cancer Res Treat,2007,106(1):11-17.
12 Sirnes S,Lind GE,Bruun J,et al.Connexins in colorectal cancer pathogenesis[J].Int J Cancer,2015,137(1):1-11.
13 Yang J,Qin G,Luo M,et al.Reciprocal positive regulation between Cx26 and PI3K/Akt pathway confers acquired gefitinib resistance in NSCLC cells via GJIC-independent induction of EMT[J].Cell Death Dis,2015,6(7):e1829-e1840.
14 Ito A,Koma Y,Uchino K,et al.Increased expression of connexin 26 in the invasive component of lung squamous cell carcinoma:significant correlation with poor prognosis[J].Cancer Lett,2006,234(2):239-248.
15 Inose T,Kato H,Kimura H,et al.Correlation between connexin 26 expression and poor prognosis of esophageal squamous cell carcinoma[J].Ann Surg Oncol,2009,16(6):1704-1710.
16 Fu YR,Luo Y,Xie X,et al.Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system suppresses tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models[J].Eur Rev Med Pharmacol Sci,2019,23(17):7338-7349.
17 Sulkowska U,Wincewicz A,Kanczuga-Koda L,et al.Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma[J].Gynecol Endocrinol,2015,31(8):604-608.
18 Haass NK,Ripperger D,Wladykowski E,et al.Melanoma progression exhibits a significant impact on connexin expression patterns in the epidermal tumor microenvironment[J].Histochem Cell Biol,2010,133(1):113-124.
19 Kanczuga-Koda L,Sulkowski S,Lenczewski A,et al.Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer[J].J Clin Pathol,2006,59(4):429-433.
20 Tanaka M,Grossman H.Connexin 26 gene therapy of human bladder cancer:induction of growth suppression,apoptosis,and synergy with Cisplatin[J].Hum Gene Ther,2001,12(18):2225-2236.
21 Chandrasekhar A,Kalmykov EA,Polusani SR,et al.Intercellular redistribution of cAMP underlies selective suppression of cancer cell growth by connexin26[J].PLoS One,2013,8(12):82335-82352.
22 Thiagarajan PS,Sinyuk M,Turaga SM,et al.Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase[J].Nat Commun,2018,9(1):578-591.
23 Liu XL,Furuya T,Li D,et al.Connexin 26 expression correlates with less aggressive phenotype of intestinal type-gastric carcinomas[J].Int J Mol Med,2010,25(5):709-716.
24 Nomura S,Maeda K,Noda E,et al.Clinical significance of the expression of connexin26 in colorectal cancer[J].J Exp Clin Cancer Res,2010,29(1):79-84.
25 Leithe E.Regulation of connexins by the ubiquitin system:Implications for intercellular communication and cancer[J].Biochim Biophys Acta,2016,1865(2):133-146.
26 Polusani SR,Kalmykov EA,Chandrasekhar A,et al.Cell coupling mediated by connexin 26 selectively contributes to reduced adhesivity and increased migration[J].J Cell Sci,2016,129(23):4399-4410.
27 Stoletov K,Strnadel J,Zardouzian E,et al.Role of connexins in metastatic breast cancer and melanoma brain colonization[J].J Cell Sci,2013,126(Pt 4):904-913.
28 Ezumi K,Yamamoto H,Murata K,et al.Aberrant expression of connexin 26 is associated with lung metastasis of colorectal cancer[J].Clin Cancer Res,2008,14(3):677-684.
29 Naoi Y,Miyoshi Y,Taguchi T,et al.Connexin26 expression is associated with aggressive phenotype in human papillary and follicular thyroid cancers[J].Cancer Lett,2008,262(2):248-256.
30 Li X,Su Y,Pan J,et al.Connexin 26 is down-regulated by KDM5B in the progression of bladder cancer[J].Int J Mol Sci,2013,14(4):7866-7879.
31 Teleki I,Krenacs T,Szasz MA,et al.The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer[J].BMC Cancer,2013,13(1):50-62.
32 Tang Y,Zhang YJ,Wu ZH.High GJB2 mRNA expression and its prognostic significance in lung adenocarcinoma:a study based on the TCGA database[J].Medicine,2020,99(14):e19054-e19060.
33 Kandouz M,Batist G.Gap junctions and connexins as therapeutic targets in cancer[J].Expert Opin Ther Targets,2010,14(7):681-692.
34 Jindal S,Chockalingam S,Ghosh S,et al.Connexin and gap junctions:perspectives from biology to nanotechnology based therapeutics[J].Transl Res,2021:144-167.
35 Garcia-Rodríguez L,Pérez-Torras S,Carrió M,et al.Connexin-26 is a key factor mediating gemcitabine bystander effect[J].Mol Cancer Ther,2011,10(3):505-517.
36 Luo H,Wang X,Ge H,et al.Inhibition of ubiquitin-specific protease 14 promotes connexin 32 internalization and counteracts cisplatin cytotoxicity in human ovarian cancer cells[J].Oncol Rep,2019,42(3):1237-1247.

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