Oncogenic function of TUSC3 in non-small cell lung cancer is associated with Hedgehog signalling pathway
Oncogenic function of TUSC3 in non-small cell lung cancer is associated with Hedgehog signalling pathway
复制标题
TUSC3在非小细胞肺癌中的致癌功能与Hedgehog信号通路相关
DOI：
10.1016/j.bbadis.2017.05.005
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发表时间：
2017-07-01
影响因子：
6.2
通讯作者：
Lin, Jie
中科院分区：
文献类型：
--
作者：
Gu, Ye;Pei, Xiaojuan;Lin, Jie
非小细胞肺癌（NSCLC）占所有肺癌的75-80%，是最常见的癌症死亡原因。候选肿瘤抑制因子3 （TUSC3）在许多生化功能和细胞学过程中起关键作用。在上皮癌中经常观察到TUSC3的失调。在本研究中，我们观察到与邻近非肿瘤肺组织相比，临床NSCLC样本中TUSC3 mRNA和蛋白水平的表达上调。TUSC3的表达水平与肿瘤转移及患者生存有显著相关性。在非小细胞肺癌细胞中，TUSC3的过表达导致体外增殖、迁移和侵袭增加，并加速体内异种移植物肿瘤的生长，而在TUSC3沉默的细胞中则相反。western blotting观察到TUSC3过表达细胞中GLI1、SMO、PTCH1和PTCH2丰度升高。免疫共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，我们的研究证实了TUSC3在NSCLC中的致癌作用，并表明TUSC3的失调可能通过参与Hedgehog （Hh）信号通路影响肿瘤细胞的侵袭和迁移。
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.