喉癌患者癌组织与癌旁正常组织之间蛋白磷酸酶2A及其相关分子标志物表达水平的比较研究（英文）
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摘要
目的:探讨喉癌患者组织样本中蛋白磷酸酶2A及其相关蛋白在癌组织与癌旁组织之间的表达差异,建立可用于临床进行喉癌患者预后分层的多指标预测体系。创新点:以蛋白磷酸酶2A为核心,探讨系列肿瘤转移相关指标参与喉癌发生发展的分子机制。方法:收集2012～2015年间浙江大学医学院附属第二医院耳鼻咽喉科28例喉鳞状细胞癌患者的临床组织样本,提取总蛋白后进行免疫印迹分析。结论:与癌旁正常组织相比,喉癌组织中phosphoPP2A/C(Y307)、α4、CIP2A、Akt、ezrin、phosphoezrin(T567)、14-3-3以及FAK蛋白水平均显著升高,而phospho-Akt(T308)蛋白水平则显著降低。
引文
Cau Y,Valensin D,Mori M,et al.,2018.Structure,function,involvement in diseases and targeting of 14-3-3 proteins:an update.Curr Med Chem,25(1):5-21.https://doi.org/10.2174/0929867324666170426095015
Chen LP,Lai YD,Li DC,et al.,2011.α4 is highly expressed in carcinogen-transformed human cells and primary human cancers.Oncogene,30(26):2943-2953.https://doi.org/10.1038/onc.2011.20
Kauko O,O'Connor CM,Kulesskiy E,et al.,2018.PP2Ainhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells.Sci Transl Med,10(450):eaaq1093.https://doi.org/10.1126/scitranslmed.aaq1093
Kiely M,Kiely PA,2015.PP2A:the wolf in sheep’s clothing?Cancers,7(2):648-669.https://doi.org/10.3390/cancers7020648
Kozakiewicz P,Grzybowska-Szatkowska L,2018.Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma.Oncol Lett,15(5):7497-7505.https://doi.org/10.3892/ol.2018.8300
Liu JH,Wang BL,Huang P,et al.,2016a.Microcystin-LRpromotes cell proliferation in the mice liver by activating Akt and P38/ERK/JNK cascades.Chemosphere,163:14-21.https://doi.org/10.1016/j.chemosphere.2016.08.002
Liu JH,Wang H,Wang BL,et al.,2016b.Microcystin-LRpromotes proliferation by activating Akt/S6K1 pathway and disordering apoptosis and cell cycle associated proteins phosphorylation in HL7702 cells.Toxicol Lett,240(1):214-225.https://doi.org/10.1016/j.toxlet.2015.10.015
Mc Clatchey AI,2014.ERM proteins at a glance.J Cell Sci,127:3199-3204.https://doi.org/10.1242/jcs.098343
Morrison DK,2009.The 14-3-3 proteins:integrators of diverse signaling cues that impact cell fate and cancer development.Trends Cell Biol,19(1):16-23.https://doi.org/10.1016/j.tcb.2008.10.003
Ouchida AT,Uyemura VT,Queiroz AL,et al.,2019.SETprotein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy.Biochim Biophys Acta,1866(4):623-637.https://doi.org/10.1016/j.bbamcr.2019.01.005
Sulzmaier FJ,Jean C,Schlaepfer DD,2014.FAK in cancer:mechanistic findings and clinical applications.Nat Rev Cancer,14(9):598-610.https://doi.org/10.1038/nrc3792
Ventel?S,Sittig E,Mannermaa L,et al.,2015.CIP2A is an Oct4 target gene involved in head and neck squamous cell cancer oncogenicity and radioresistance.Oncotarget,6(1):144-158.https://doi.org/10.18632/oncotarget.2670
Wang BL,Liu JH,Huang P,et al.,2017.Protein phosphatase2A inhibition and subsequent cytoskeleton reorganization contributes to cell migration caused by microcystin-LR in human laryngeal epithelial cells(Hep-2).Environ Toxicol,32(3):890-903.https://doi.org/10.1002/tox.22289
Wang H,Liu JH,Lin SY,et al.,2014.MCLR-induced PP2A inhibition and subsequent rac1 inactivation and hyperphosphorylation of cytoskeleton-associated proteins are involved in cytoskeleton rearrangement in SMMC-7721 human liver cancer cell line.Chemosphere,112:141-153.https://doi.org/10.1016/j.chemosphere.2014.03.130
Wang HY,Xu KL,Wang BL,et al.,2017.Microcystin-LRinduces a wide variety of biochemical changes in the A549 human non-small cell lung cancer cell line:roles for protein phosphatase 2A and its substrates.Environ Toxicol,32(3):1065-1078.https://doi.org/10.1002/tox.22305
Chen LP,Lai YD,Li DC,et al.,2011.α4 is highly expressed in carcinogen-transformed human cells and primary human cancers.Oncogene,30(26):2943-2953.https://doi.org/10.1038/onc.2011.20
Kauko O,O'Connor CM,Kulesskiy E,et al.,2018.PP2Ainhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells.Sci Transl Med,10(450):eaaq1093.https://doi.org/10.1126/scitranslmed.aaq1093
Kiely M,Kiely PA,2015.PP2A:the wolf in sheep’s clothing?Cancers,7(2):648-669.https://doi.org/10.3390/cancers7020648
Kozakiewicz P,Grzybowska-Szatkowska L,2018.Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma.Oncol Lett,15(5):7497-7505.https://doi.org/10.3892/ol.2018.8300
Liu JH,Wang BL,Huang P,et al.,2016a.Microcystin-LRpromotes cell proliferation in the mice liver by activating Akt and P38/ERK/JNK cascades.Chemosphere,163:14-21.https://doi.org/10.1016/j.chemosphere.2016.08.002
Liu JH,Wang H,Wang BL,et al.,2016b.Microcystin-LRpromotes proliferation by activating Akt/S6K1 pathway and disordering apoptosis and cell cycle associated proteins phosphorylation in HL7702 cells.Toxicol Lett,240(1):214-225.https://doi.org/10.1016/j.toxlet.2015.10.015
Mc Clatchey AI,2014.ERM proteins at a glance.J Cell Sci,127:3199-3204.https://doi.org/10.1242/jcs.098343
Morrison DK,2009.The 14-3-3 proteins:integrators of diverse signaling cues that impact cell fate and cancer development.Trends Cell Biol,19(1):16-23.https://doi.org/10.1016/j.tcb.2008.10.003
Ouchida AT,Uyemura VT,Queiroz AL,et al.,2019.SETprotein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy.Biochim Biophys Acta,1866(4):623-637.https://doi.org/10.1016/j.bbamcr.2019.01.005
Sulzmaier FJ,Jean C,Schlaepfer DD,2014.FAK in cancer:mechanistic findings and clinical applications.Nat Rev Cancer,14(9):598-610.https://doi.org/10.1038/nrc3792
Ventel?S,Sittig E,Mannermaa L,et al.,2015.CIP2A is an Oct4 target gene involved in head and neck squamous cell cancer oncogenicity and radioresistance.Oncotarget,6(1):144-158.https://doi.org/10.18632/oncotarget.2670
Wang BL,Liu JH,Huang P,et al.,2017.Protein phosphatase2A inhibition and subsequent cytoskeleton reorganization contributes to cell migration caused by microcystin-LR in human laryngeal epithelial cells(Hep-2).Environ Toxicol,32(3):890-903.https://doi.org/10.1002/tox.22289
Wang H,Liu JH,Lin SY,et al.,2014.MCLR-induced PP2A inhibition and subsequent rac1 inactivation and hyperphosphorylation of cytoskeleton-associated proteins are involved in cytoskeleton rearrangement in SMMC-7721 human liver cancer cell line.Chemosphere,112:141-153.https://doi.org/10.1016/j.chemosphere.2014.03.130
Wang HY,Xu KL,Wang BL,et al.,2017.Microcystin-LRinduces a wide variety of biochemical changes in the A549 human non-small cell lung cancer cell line:roles for protein phosphatase 2A and its substrates.Environ Toxicol,32(3):1065-1078.https://doi.org/10.1002/tox.22305