p53-inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma.
p53-inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma.
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p53诱导基因3通过激活肺腺癌中的FAK/Src通路促进细胞迁移和侵袭
DOI：
10.1111/cas.13818
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发表时间：
2018-12
期刊：
影响因子：
5.7
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Gu MM;Gao D;Yao PA;Yu L;Yang XD;Xing CG;Zhou J;Shang ZF;Li M
p53诱导基因3（PIG 3）是p53诱导的凋亡启动基因之一，在细胞凋亡和DNA损伤反应中起重要作用。我们先前的研究报告了PIG 3的致癌作用与非小细胞肺癌（NSCLC）的肿瘤进展和转移相关。本研究进一步分析了504例肺腺癌（LUAD）和501例肺鳞状细胞癌（LUSC）组织中PIG 3 mRNA的表达，发现有淋巴结转移的LUAD组织中PIG 3的表达显著高于无淋巴结转移的LUAD组织，而LUSC组织中PIG 3的表达在有淋巴结转移和无淋巴结转移的样本中无差异。进行功能获得和丧失实验以证实PIG 3在体外的转移作用，并探索其在NSCLC转移中的致癌作用的机制。结果显示，PIG 3基因敲低可显著抑制NSCLC细胞的迁移和侵袭能力，并降低桩蛋白、磷酸化粘着斑激酶（FAK）和磷酸化Src激酶的表达，而其过表达则产生相反的作用。用FAK抑制剂阻断FAK可逆转NSCLC细胞中PIG 3过表达诱导的细胞运动性，表明PIG 3通过FAK/Src/桩蛋白途径增加细胞转移。此外，PIG 3沉默使NSCLC细胞对FAK抑制剂敏感。总之，我们的数据揭示了PIG 3在诱导LUAD转移中的作用，以及其作为新的FAK调节剂的作用，这表明它可以被认为是治疗LUAD转移的新的预后生物标志物或治疗靶点。
The p53‐inducible gene 3 (PIG3) is one of the p53‐induced genes at the onset of apoptosis, which plays an important role in cell apoptosis and DNA damage response. Our previous study reported an oncogenic role of PIG3 associated with tumor progression and metastasis in non‐small cell lung cancer (NSCLC). In this study, we further analyzed PIG3 mRNA expression in 504 lung adenocarcinoma (LUAD) and 501 lung squamous cell carcinoma (LUSC) tissues from The Cancer Genome Atlas database and we found that PIG3 expression was significantly higher in LUAD with lymph node metastasis than those without, while no difference was observed between samples with and without lymph node metastasis in LUSC. Gain and loss of function experiments were performed to confirm the metastatic role of PIG3 in vitro and to explore the mechanism involved in its oncogenic role in NSCLC metastasis. The results showed that PIG3 knockdown significantly inhibited the migration and invasion ability of NSCLC cells, and decreased paxillin, phospho‐focal adhesion kinase (FAK) and phospho‐Src kinase expression, while its overexpression resulted in the opposite effects. Blocking FAK with its inhibitor reverses PIG3 overexpression‐induced cell motility in NSCLC cells, indicating that PIG3 increased cell metastasis through the FAK/Src/paxillin pathway. Furthermore, PIG3 silencing sensitized NSCLC cells to FAK inhibitor. In conclusion, our data revealed a role for PIG3 in inducing LUAD metastasis, and its role as a new FAK regulator, suggesting that it could be considered as a novel prognostic biomarker or therapeutic target in the treatment of LUAD metastasis.
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影响因子：
11.2
作者：
Crompton, Brian D.;Carlton, Anne L.;Stegmaier, Kimberly
通讯作者：
Stegmaier, Kimberly
DOI：
10.1016/j.bbrc.2013.12.124
发表时间：
2014-01-24
影响因子：
3.1
作者：
Guan, Xiaoxiang;Liu, Zhensheng;Wang, Luo;Johnson, David G.;Wei, Qingyi
通讯作者：
Wei, Qingyi
影响因子：
16
作者：
Lim, Ssang-Taek;Chen, Xiao Lei;Llic, Dusko
通讯作者：
Llic, Dusko
影响因子：
4.6
作者：
Golubovskaya, Vita M.;Finch, Richard;Cance, William G.
通讯作者：
Cance, William G.
DOI：
10.1016/j.bbaexp.2004.03.002
发表时间：
2004-05-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Golubovskaya, V;Kaur, A;Cance, W
通讯作者：
Cance, W