P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.
P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.
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DOI：
10.1111/cas.13009
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发表时间：
2016-10
期刊：
影响因子：
5.7
通讯作者：
Saiki I
中科院分区：
文献类型：
--
作者：
Kato S;Yokoyama S;Hayakawa Y;Li L;Iwakami Y;Sakurai H;Saiki I
虽然分泌性基质细胞蛋白结缔组织生长因子（CTGF）已被报道与肺癌转移有关，但CTGF调节肺癌转移的确切机制尚未阐明。在本研究中，我们显示了CTGF分泌和p38通路在非小细胞肺癌（NSCLC）侵袭和转移潜力中的分子联系。在三种不同的人NSCLC细胞系（PC-14、A549和PC-9）中，它们的体外侵袭力与CTGF分泌水平呈负相关。通过补充或减少NSCLC培养物中的CTGF分泌，NSCLC细胞系的侵袭和转移潜能的失调在很大程度上得到补偿。通过关注已知由CTGF调节的蛋白激酶，我们发现p38通路是CTGF调节NSCLC转移潜能的关键下游信号。重要的是，在癌症基因组图谱肺腺癌数据集中鉴定了CTGF和p38磷酸化状态之间的负相关性。在我们的研究结果的临床意义的背景下，我们表明，p38抑制剂，SB 203580，降低了非小细胞肺癌分泌低水平的CTGF的转移潜力。总的来说，我们目前的研究结果表明，CTGF/p38轴是NSCLC转移，特别是分泌低水平CTGF的NSCLC的新的治疗靶点。
Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non‐small‐cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC‐14, A549, and PC‐9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF.
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影响因子：
3.7
作者：
Wolf A;Beuerlein K;Eckart C;Weiser H;Dickkopf B;Müller H;Sakurai H;Kracht M
通讯作者：
Kracht M
DOI：
10.1165/ajrcmb.26.5.4689
发表时间：
2002-05-01
影响因子：
6.4
作者：
Greenberg, AK;Basu, S;Lee, TC
通讯作者：
Lee, TC
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作者：
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影响因子：
2.9
作者：
Matsunaga, Atsushi;Ishii, Yoshiyuki;Kitagawa, Yuko
通讯作者：
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影响因子：
11.2
作者：
Kikuchi, Ryoko;Tsuda, Hitoshi;Imoto, Issei
通讯作者：
Imoto, Issei