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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Oncogenic function of TUSC3 in non-small cell lung cancer is associated with Hedgehog signalling pathway
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Oncogenic function of TUSC3 in non-small cell lung cancer is associated with Hedgehog signalling pathway

机译:TUSC3在非小细胞肺癌中的致癌功能与刺猬信号通路相关

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摘要

Non-small cell lung cancer (NSCLC) represents 75-80% of all lung carcinomas, which is the most common cause of death from cancer. Tumour suppressor candidate 3 (TUSC3) is pivotal in many biochemical functions and cytological processes. Dis-regulation of TUSC3 is frequently observed in epithelial cancers. In this study, we observed up-regulated TUSC3 expression at the mRNA and protein levels in clinical NSCLC samples compared with adjacent non-tumorous lung tissues. The expression level of TUSC3 is significantly correlated with tumour metastasis and patient survival. Overexpression of TUSC3 in NSCLC cells led to increased proliferation, migration, and invasion in vitro and accelerated xenograft tumour growth in vivo, while the opposite effects were achieved in TUSC3-silenced cells. Increased GLI1, SMO, PTCH1, and PTCH2 abundance were observed in TUSC3 overexpressed cells using western blotting. Co-immunoprecipitation and immunofluorescence analyses further revealed interaction between TUSC3 and GLI1. In conclusion, our study demonstrated an oncogenic role of TUSC3 in NSCLC and showed that dis-regulation of TUSC3 may affect tumour cell invasion and migration through possible involvement in the Hedgehog (Hh) signalling pathway.
机译:非小细胞肺癌(NSCLC)代表所有肺癌的75-80%,这是癌症中最常见的死亡原因。肿瘤抑制剂候选3(TUSC3)在许多生物化学功能和细胞学过程中是枢转的。在上皮癌中经常观察到TUSC3的分解。在这项研究中,与相邻的非肿瘤肺组织相比,我们观察到临床NSCLC样品中mRNA和蛋白质水平的上调TUSC3表达。 TUSC3的表达水平与肿瘤转移和患者存活率显着相关。在NSCLC细胞中的TUSC3的过度表达导致体外体外增殖,迁移和侵袭,并加速异种移植肿瘤生长在体内,而在TUSC3-沉默的细胞中实现了相反的影响。使用Western Blotting在TUSC3过表达细胞中观察到GLI1,SMO,PTCH1和PTCH2丰度。共免疫沉淀和免疫荧光分析进一步揭示了TUSC3和GLI1之间的相互作用。总之,我们的研究证明了TUSC3在NSCLC中的致癌作用,并显示TUSC3的分解可能会影响肿瘤细胞侵袭和通过可能参与刺猬(HH)信号通路的迁移。

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  • 作者单位

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Thorac Surg Guangzhou 510515 Guangdong Peoples R China;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Shenzhen Peoples Hosp Dept Pathol Shenzhen 510820 Peoples R China;

    Shenzhen Peoples Hosp Dept Pathol Shenzhen 510820 Peoples R China;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

    Southern Med Univ Nanfang Hosp Dept Pathol 1838 Guangzhou Ave Guangzhou 510515 Guangdong;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    TUSC3; NSCLC; Hh signalling pathway;

    机译:TUSC3;NSCLC;HH信号通路;

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