Extracellular gamma-synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion.
Extracellular gamma-synuclein promotes tumor cell motility by activating β1 integrin-focal adhesion kinase signaling pathway and increasing matrix metalloproteinase-24, -2 protein secretion.
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细胞外γ-突触核蛋白通过激活β1整合素-焦点粘附激酶信号通路和增加基质金属蛋白酶-24、-2蛋白分泌来促进肿瘤细胞运动
DOI：
10.1186/s13046-018-0783-6
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发表时间：
2018-06-15
期刊：
影响因子：
--
通讯作者：
Shou C
中科院分区：
文献类型：
--
作者：
Liu C;Qu L;Zhao C;Shou C
越来越多的证据表明，γ -突触核蛋白（SNCG）水平与多种人类癌症的侵袭和转移有显著相关性。我们前期的研究表明，SNCG可以分泌到细胞外环境，促进肿瘤细胞运动，但其作用机制尚不清楚。通过免疫组织化学染色、免疫荧光染色和结直肠癌（CRC）细胞膜分离鉴定SNCG的膜结合能力。通过共免疫沉淀和far Western blot验证SNCG与β1整合素的相关性。在抑制β1整合素和局灶黏附激酶（FAK）后，采用transwell室法检测SNCG对细胞运动的影响，Western blot检测蛋白水平的变化。通过Spearman秩相关分析确定人结直肠癌组织中SNCG与活化β1整合素水平的关系。用抗体阵列法筛选条件培养基（CM）分泌蛋白。结直肠癌细胞膜上细胞外SNCG结合β1整合素，激活β1整合素和FAK水平升高。相应地，sncg增强的细胞运动性通过敲低或抑制β1整合素或FAK而被抵消。进一步研究发现，SNCG水平高预示预后不良，且SNCG水平与人CRC组织中活化β1整合素和磷酸化fak （Tyr397）水平呈正相关。此外，细胞外SNCG促进HCT116细胞中纤维连接蛋白（FN）、玻璃体连接蛋白（VN）、基质金属蛋白酶(MMP)-2和MMP-24的分泌。SNCG可提高HCT116细胞CM中MMP-2的蛋白酶活性，而抑制β1整合素可使MMP-2蛋白酶活性降低。我们的研究结果强调了SNCG在重塑CRC细胞外微环境和诱导β1整合素- fak信号通路中的潜在作用。本文的在线版本（10.1186/s13046-018-0783-6）包含补充资料，仅供授权用户使用。
Increasing evidence reveals a significant correlation between gamma-synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane. Association between SNCG and β1 integrin was validated by coimmunoprecipitation and far Western blot. After inhibition of β1 integrin and focal adhesion kinase (FAK), effect of SNCG on cell motility was measured by transwell chamber assays and changes of protein levels were detected by Western blot. Association between SNCG and activated β1 integrin levels in human CRC tissues was determined by Spearman’s rank correlation analysis. Secreted proteins in conditioned medium (CM) were screened by antibody array. Extracellular SNCG bound β1 integrin on CRC cell membrane and increased levels of activated β1 integrin and FAK. Correspondingly, SNCG-enhanced cell motility was counteracted by knockdown or inhibition of β1 integrin or FAK. Further study revealed that high SNCG level indicated poor outcome and SNCG levels positively correlated with those of activated β1 integrin and phospho-FAK (Tyr397) in human CRC tissues. Additionally, extracellular SNCG promoted secretion of fibronectin (FN), vitronectin (VN), matrix metalloproteinase (MMP)-2, and MMP-24 from HCT116 cells. Protease activity of MMP-2 in the CM of HCT116 cells was increased by treatment with SNCG, which was abolished by inhibiting β1 integrin. Our results highlight the potential role of SNCG in remodeling extracellular microenvironment and inducing β1 integrin-FAK signal pathway of CRC cells. The online version of this article (10.1186/s13046-018-0783-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
Druecker, Patrick;Pejic, Milena;Gerke, Volker
通讯作者：
Gerke, Volker
hTERT通过增强FOXO3a泛素化和随后的ITGB1上调促进胃癌细胞的侵袭
影响因子：
24.5
作者：
Hu, Changjiang;Ni, Zhenghong;Yang, Shi-ming
通讯作者：
Yang, Shi-ming
影响因子：
4.8
作者：
Bouvard, D;Vignoud, L;Block, MR
通讯作者：
Block, MR
DOI：
10.1007/978-1-4939-2694-7_38
发表时间：
2015-01-01
期刊：
WESTERN BLOTTING: METHODS AND PROTOCOLS
影响因子：
--
作者：
Jadwin, Joshua A.;Mayer, Bruce J.;Machida, Kazuya
通讯作者：
Machida, Kazuya
影响因子：
3.1
作者：
Liu, Caiyun;Qu, Like;Shou, Chengchao
通讯作者：
Shou, Chengchao