FBXW7在非小细胞肺癌治疗耐药中的研究进展
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摘要
非小细胞肺癌(non-small cell lung cancer,NSCLC)是全球范围内最常见的恶性肿瘤之一。NSCLC治疗耐药严重影响了预后,研究NSCLC治疗耐药的分子机制非常必要。泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)能够通过选择性降解短期蛋白调节细胞内重要过程,如周期调控、转录调控、信号转导、凋亡和分化等,其表达的异常影响肿瘤的发生、发展及预后。F-box家族蛋白是UPS的重要组成部分,而F框/WD-40域蛋白7(F-box and WD-40 domain protein 7,FBXW7)是F-box家族蛋白中研究的经典蛋白之一。研究表明FBXW7与NSCLC耐药有关,主要机制是FBXW7突变减少其下游蛋白的泛素化降解,导致NSCLC患者药物治疗耐药,其下游蛋白包括Snail蛋白、骨髓细胞白血病因子1(myeloid cell leukemia sequence 1,MCL-1)、雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)、卷曲螺旋结构域6(coiled-coil-domain containing 6,CCDC6)。雷帕霉素、组蛋白脱乙酰酶抑制剂MS-275及冬凌草素对治疗耐药的FBXW7突变的NSCLC患者有效。
Non-small cell lung cancer(NSCLC) is one of the most common malignant tumors in the world.NSCLC shows serious effect on prognosis for drug resistance,and it is necessary to study the molecular mechanism for drug resistance in NSCLC.Ubiquitin-proteasome system(UPS) can regulate some important cellular processes by degrading short-term protein,and the abnormal expression is closely related to the occurrence,development and prognosis of tumor.The F-box family protein is an important component of the ubiquitin proteasome,such as cycle regulation,transcriptional regulation,signal transduction,apoptosis and differentiation.F-box and WD-40 domain protein 7(FBXW7) is just the classic protein components among F-box family protein.Studies have shown that FBXW7 is related to drug resistance in NSCLC.The main mechanism is that FBXW7 mutation leads to drug resistance by reducing ubiquitination and degradation of its downstream proteins,including Snail protein,myeloid cell leukemia sequence 1(MCL-1),mammalian target of rapamycin(mTOR),and coiled-coil-domain containing 6(CCDC6).Rapamycin,histone deacetylase inhibitor MS-275,and rabdosia are effective in drug-resistant NSCLC patients with FBXW7 mutation.
Non-small cell lung cancer(NSCLC) is one of the most common malignant tumors in the world.NSCLC shows serious effect on prognosis for drug resistance,and it is necessary to study the molecular mechanism for drug resistance in NSCLC.Ubiquitin-proteasome system(UPS) can regulate some important cellular processes by degrading short-term protein,and the abnormal expression is closely related to the occurrence,development and prognosis of tumor.The F-box family protein is an important component of the ubiquitin proteasome,such as cycle regulation,transcriptional regulation,signal transduction,apoptosis and differentiation.F-box and WD-40 domain protein 7(FBXW7) is just the classic protein components among F-box family protein.Studies have shown that FBXW7 is related to drug resistance in NSCLC.The main mechanism is that FBXW7 mutation leads to drug resistance by reducing ubiquitination and degradation of its downstream proteins,including Snail protein,myeloid cell leukemia sequence 1(MCL-1),mammalian target of rapamycin(mTOR),and coiled-coil-domain containing 6(CCDC6).Rapamycin,histone deacetylase inhibitor MS-275,and rabdosia are effective in drug-resistant NSCLC patients with FBXW7 mutation.
引文
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[27]Min SH,Lau AW,Lee TH,et al.Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase[J].Mol Cell,2012,46(6):771-783.
[28]Han J,Zhao F,Zhang J,et al.MiR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway[J].Int JOncol,2016,48(5):1855-1867.
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[30]Theys J,Yahyanejad S,Habets R,et al.High NOTCH activity induces radiation resistance in non-small cell lung cancer[J].Radiother Oncol,2013,108(3):440-445.
[31]Shen H,Guan D,Shen J,et al.TGF-β1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN[J].Biomed Pharmacother,2016,77(1):1-6.
[32]Hu Y,Hong Y,Xu Y,et al.Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC[J].Apoptosis,2014,19(11):1627-1636.
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[34]Kobayashi S,Boggon TJ,Dayaram T,et al.EGFR mutation and resistance of non-small cell lung cancer to gefitinib[J].N Engl J Med2016,352(8):786-792.
[35]Katayama R,Shaw AT,Khan TM,et al.Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers[J].Sci Transl Med,2012,4(120):120ra17.
[36]Engelman JA,Zejnullahu K,Mitsudomi T,et al.MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3signaling[J].Science,2007,316(5827):1039-1043.
[37]Gombodorj N,Yokobori T,Tanaka N,et al.Correlation between high FBXW7 expression in pretreatment biopsy specimensand good response to chemoradiation therapy in patients with locally advanced esophageal cancer:A retrospective study[J].J Surg Oncol,2018118(1):101-108.
[38]Lin J,Ji A,Qiu G,et al.FBW7 is associated with prognosis,inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells[J].Cancer Sci,2018,109(4):1001-1011.
[39]Yeung KT,Yang J.Epithelial-mesenchymal transition in tumor metastasis[J].Mol Oncol,2017,11(1):28-39.
[40]Yu HG,Wei W,Xia LH,et al.FBW7 upregulation enhances cisplatin cytotoxicity in non-small cell lung cancer cells[J].Asian Pac J Cancer Prev,2013,14(11):6321-6326.
[41]Zhang Y,Zhang X,Zhao S,et al.FBW7 loss promotes epithelial-tomesenchymal transition in non-small cell lung cancer through the stabilization of Snail protein[J].Cancer Lett,2018,419(8):75-83.
[42]Leverson JD,Zhang H,Chen J,et al.Potent and selective smallmolecule MCL-1inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263(navitoclax)[J].Cell Death Dis,2015,6(1):e1590.
[43]Lin KH,Winter PS,Xie A,et al.Targeting MCL-1/BCL-XLforestalls the acquisition of resistance to ABT-199 in acute myeloid leukemia[J].Sci Rep,2016,6:27696.
[44]Wertz IE,Kusam S,Lam C,et al.Sensitivity to antitubulin chemotherapeutics is regulated by MCL-1 and FBW7[J].Nature2011,71(7336):110-114.
[45]Ye M,Zhang Y,Zhang X,et al.Targeting FBXW7 as a strategy to overcome resistance to targeted therapy in non-small cell lung cancer[J].Cancer Res,2017,77(13):3527-3593.
[46]Zhang H,Chen F,He Y,et al.Sensitivity of non-small cell lung cancer to erlotinib is regulated by the Notch/miR-223/FBXW7 pathway[J]Biosci Rep,2017,37(3):BSR20160478.
[47]Xiao Y,Yin C,Wang Y,et al.FBXW7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy[J]Mol Oncol,2018,12(6):883-895.
[48]Morra F,Luise C,Visconti R,et al.New therapeutic perspectives in CCDC6 deficient lung cancer cells[J].Int J Cancer,2015,136(9):2146-2157.
[49]Zhao J,Tang J,Men W,et al.FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells[J].FEBS Lett,2012,586(24):4257-4263.
[50]Morra F,Luise C,Merolla F,et al.FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC[J].Oncotarget,2015,6(14):12697-12709.
[51]He L,Torres-Lockhart K,Forster N,et al.Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and Bcl-2 inhibitor synergy in squamous cell carcinoma[J].Cancer Discov,2013,3(3):324-337.
[52]Villaruz LC,Socinski MA.Temsirolimus therapy in a patient with lung adenocarcinoma harboring an FBXW7 mutation[J].Lung Cancer,2014,83(2):300-301.
[53]Yokobori T,Yokoyama Y,Mogi A,et al.FBXW7 mediates chemotherapeutic sensitivity and prognosis in NSCLCs[J].Mol Res2014,12(1):32-37.
[2]Hershko A.The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle[J].Cell Death Differ,2005,12(9):1191-1197.
[3]Zhou W,Wei W,Sun Y.Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein(SCF)E3 ubiquitin ligases[J].Cell Res,2013,23(5):599-619.
[4]Cardozo T,Pagano M.The SCF ubiquitin ligase:insights into a molecular machine[J].Nat Rev Mol Cell Biol,2004,5(9):739-751.
[5]Wang Z,Liu P,Inuzuka H,et al.Roles of F-box proteins in cancer[J]Nat Rev Cancer,2014,14(4):233-247.
[6]Cao J,Ge MH,Ling ZQ.Fbxw7 tumor suppressor:A vital regulator contributes to human tumorigenesis[J].Medicine(Baltimore)2016,95(7):e2496.
[7]Xu J,Wu W,Wang J,et al.MiR-367 promotes the proliferation and invasion of non-small cell lung cancer via targeting FBXW7[J]Oncol Rep,2017,37(2):1052-1058.
[8]Chang H,Liu YH,Wang LL,et al.MiR-182 promotes cell proliferation by suppressing FBXW7 and FBXW11 in non-small cell lung cancer[J].Am J Transl Res,2018,10(4):1131-1142.
[9]Spruck CH,Strohmaier H,Sangfelt O.hCDC4 gene mutations in endometrial cancer[J].Cancer Res,2002,62(16):4535-4539.
[10]Crusio KM,King B,Reavie LB,et al.The ubiquitous nature of cancer:the role of the SCF(Fbw7)complex in development and transformation[J].Oncogene,2010,29(35):4865-4873.
[11]Welcker M,Orian A,Grim JE,et al.A nucleolar isoform of the Fbw7ubiquitin ligase regulates c-Myc and cell size[J].Curr Biol,200415(24):1852-1857.
[12]Ye X,N a l e p a G,We l c k e r M,e t a l.R e c o g n i t i o n o f phosphodegronmotifs in human cyclinE by the ScFFbw7 ubiquitin ligase[J].J Biol Chem,2004,279(48):50110-50119.
[13]Zhang W,Koepp DM.Fbw7 isoform interaction contributes to cyclin E proteolysis[J].Mol Cancer Res,2006,4(12):935-943.
[14]Tang X,Orlicky S,Lin Z,et al.Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination[J].Cell,2007,129(6):1165-1176.
[15]Kimura T,Gotoh M,Nakamura Y,et al.hCDC4b,a regulator ofcyclin E,as a direct transcriptional target of p53[J].Cancer Sci,200394(5):431-436.
[16]Xu W,Taranets L,Popov N.Regulating Fbw7 on the road to cancer[J].Semin Cancer Biol,2016,36:62-70.
[17]Yeh CH,Bellon M,Nicot C.FBXW7:a critical tumor suppressor of human cancers[J].Mol Cancer,2018,17(1):115.
[18]Zhan P,Wang Y,Zhao S,et al.FBXW7 negatively regulates ENO1expression and function in colorectal cancer[J].Lab Invest,201595(9):995-1004.
[19]Liao SY,Chiang CW.δ/GSK3β/FBXW7αaxis promotes degradation of the ZNF322A oncoprotein to suppress lung cancerprogression[J]Oncogene,2017,36(41):5722-5733.
[20]Eto K,Iwatsuki M,Watanabe M,et al.The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway[J].Int J Cancer,2015,136(7):1537-1545.
[21]Xiang J,Hang JB,Che JM,et al.miR-25 is up-regulated in non-small cell lung cancer and promotes cell proliferation and motility by targeting FBXW7[J].Int J Clin Exp Pathol,2015,8(8):9147-9153.
[22]Xu J,Wu W,Wang J,et al.miR-367 promotes the proliferation and invasion of non-small cell lung cancer via targeting FBXW7[J]Oncol Rep,2017,37(2):1052-1058.
[23]Korphaisarn K,Morris VK,Overman MJ,et al.FBXW7 missense mutation:a novel negative prognostic factor in metastatic colorectal adenocarcinoma[J].Oncotarget,2017,8(24):39268-39279.
[24]Zhou X,Jin W,Jia H,et al.MiR-223 promotes the cisplatin resistance of human gastric cancer cells via regulating cell cycle by targeting FBXW7[J].J Exp Clin Cancer Res,2015,34(1):28.
[25]Sun XF,Sun JP,Hou HT,et al.MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma[J]Tumour Biol,2016,37(11):15325-15332.
[26]Youssef O,Knuuttila A,Piirila P,et al.Hotspot mutations detectable by next-generation sequencing in exhaled breath condensates from patients with kung cancer[J].Anticancer Res,2018,38(10):5627-5634.
[27]Min SH,Lau AW,Lee TH,et al.Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase[J].Mol Cell,2012,46(6):771-783.
[28]Han J,Zhao F,Zhang J,et al.MiR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway[J].Int JOncol,2016,48(5):1855-1867.
[29]Xie M,He CS,Wei SH,et al.Notch-1 contributes to epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance in non-small cell lung cancer in vitro and in vivo[J].Eur J,2013,49(16):3559-3572.
[30]Theys J,Yahyanejad S,Habets R,et al.High NOTCH activity induces radiation resistance in non-small cell lung cancer[J].Radiother Oncol,2013,108(3):440-445.
[31]Shen H,Guan D,Shen J,et al.TGF-β1 induces erlotinib resistance in non-small cell lung cancer by down-regulating PTEN[J].Biomed Pharmacother,2016,77(1):1-6.
[32]Hu Y,Hong Y,Xu Y,et al.Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC[J].Apoptosis,2014,19(11):1627-1636.
[33]Li Y,Ma C,Shi X,et al.Effect of nitric oxide synthase on multiple drug resistance is related to Wnt signaling in non-small cell lung cancer[J].Oncol Rep,2014,32(4):1703-1708.
[34]Kobayashi S,Boggon TJ,Dayaram T,et al.EGFR mutation and resistance of non-small cell lung cancer to gefitinib[J].N Engl J Med2016,352(8):786-792.
[35]Katayama R,Shaw AT,Khan TM,et al.Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers[J].Sci Transl Med,2012,4(120):120ra17.
[36]Engelman JA,Zejnullahu K,Mitsudomi T,et al.MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3signaling[J].Science,2007,316(5827):1039-1043.
[37]Gombodorj N,Yokobori T,Tanaka N,et al.Correlation between high FBXW7 expression in pretreatment biopsy specimensand good response to chemoradiation therapy in patients with locally advanced esophageal cancer:A retrospective study[J].J Surg Oncol,2018118(1):101-108.
[38]Lin J,Ji A,Qiu G,et al.FBW7 is associated with prognosis,inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells[J].Cancer Sci,2018,109(4):1001-1011.
[39]Yeung KT,Yang J.Epithelial-mesenchymal transition in tumor metastasis[J].Mol Oncol,2017,11(1):28-39.
[40]Yu HG,Wei W,Xia LH,et al.FBW7 upregulation enhances cisplatin cytotoxicity in non-small cell lung cancer cells[J].Asian Pac J Cancer Prev,2013,14(11):6321-6326.
[41]Zhang Y,Zhang X,Zhao S,et al.FBW7 loss promotes epithelial-tomesenchymal transition in non-small cell lung cancer through the stabilization of Snail protein[J].Cancer Lett,2018,419(8):75-83.
[42]Leverson JD,Zhang H,Chen J,et al.Potent and selective smallmolecule MCL-1inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263(navitoclax)[J].Cell Death Dis,2015,6(1):e1590.
[43]Lin KH,Winter PS,Xie A,et al.Targeting MCL-1/BCL-XLforestalls the acquisition of resistance to ABT-199 in acute myeloid leukemia[J].Sci Rep,2016,6:27696.
[44]Wertz IE,Kusam S,Lam C,et al.Sensitivity to antitubulin chemotherapeutics is regulated by MCL-1 and FBW7[J].Nature2011,71(7336):110-114.
[45]Ye M,Zhang Y,Zhang X,et al.Targeting FBXW7 as a strategy to overcome resistance to targeted therapy in non-small cell lung cancer[J].Cancer Res,2017,77(13):3527-3593.
[46]Zhang H,Chen F,He Y,et al.Sensitivity of non-small cell lung cancer to erlotinib is regulated by the Notch/miR-223/FBXW7 pathway[J]Biosci Rep,2017,37(3):BSR20160478.
[47]Xiao Y,Yin C,Wang Y,et al.FBXW7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy[J]Mol Oncol,2018,12(6):883-895.
[48]Morra F,Luise C,Visconti R,et al.New therapeutic perspectives in CCDC6 deficient lung cancer cells[J].Int J Cancer,2015,136(9):2146-2157.
[49]Zhao J,Tang J,Men W,et al.FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells[J].FEBS Lett,2012,586(24):4257-4263.
[50]Morra F,Luise C,Merolla F,et al.FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC[J].Oncotarget,2015,6(14):12697-12709.
[51]He L,Torres-Lockhart K,Forster N,et al.Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and Bcl-2 inhibitor synergy in squamous cell carcinoma[J].Cancer Discov,2013,3(3):324-337.
[52]Villaruz LC,Socinski MA.Temsirolimus therapy in a patient with lung adenocarcinoma harboring an FBXW7 mutation[J].Lung Cancer,2014,83(2):300-301.
[53]Yokobori T,Yokoyama Y,Mogi A,et al.FBXW7 mediates chemotherapeutic sensitivity and prognosis in NSCLCs[J].Mol Res2014,12(1):32-37.