HGF-mediated crosstalk between cancer-associated fibroblasts and MET-unamplified gastric cancer cells activates coordinated tumorigenesis and metastasis.
HGF-mediated crosstalk between cancer-associated fibroblasts and MET-unamplified gastric cancer cells activates coordinated tumorigenesis and metastasis.
复制标题
HGF 介导的癌症相关成纤维细胞和 MET 未扩增的胃癌细胞之间的串扰激活协调的肿瘤发生和转移
DOI：
10.1038/s41419-018-0922-1
复制
发表时间：
2018-08-29
影响因子：
9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Ding X;Ji J;Jiang J;Cai Q;Wang C;Shi M;Yu Y;Zhu Z;Zhang J
癌相关成纤维细胞（CAF）是肿瘤间质的重要组成部分，在肿瘤进展中起关键作用。CAFs通过多种细胞因子参与与肿瘤细胞的相互作用。在本研究中，我们筛选出肝细胞生长因子（HGF）作为主要来源于CAFs的细胞因子。CAFs来源的HGF通过激活HGF/c-Met/STAT 3/twist 1通路促进MET未扩增胃癌（GC）的增殖、迁移和侵袭。通过上调IL-6 R表达激活IL-6/IL-6 R/JAK 2/STAT 3/twist 1通路。由于IL-6也被发现上调c-Met表达，我们确定了HGF和IL-6在增强CAFs特征中的合作。体内实验表明，CAFs衍生的HGF促进MET未扩增的GC的肿瘤发生和转移。进行基因集富集分析（GSEA）以证实我们的发现。我们的研究发现，MET未扩增的GC诱导CAFs中HGF表达的增加有助于肿瘤微环境中MET未扩增的GC和CAFs的恶性表型。
Cancer-associated fibroblasts (CAFs) are important components of tumor stroma and play a key role in tumor progression. CAFs involve in crosstalk with tumor cells through various kinds of cytokines. In the present study, we screened hepatocyte growth factor (HGF) as a cytokine predominantly originating from CAFs. CAFs-derived HGF was found to promote MET-unamplified gastric cancer (GC) proliferation, migration, and invasion through the activation of HGF/c-Met/STAT3/twist1 pathway. It also activated interleukin (IL)-6/IL-6R/JAK2/STAT3/twist1 pathway by up-regulating IL-6R expression. As IL-6 was also found to upregulate c-Met expression, we identified the cooperation of HGF and IL-6 in enhancing the characteristics of CAFs. In vivo experiments revealed that CAFs-derived HGF promoted tumorigenesis and metastasis of MET-unamplified GC. Gene set enrichment analysis (GSEA) was performed to confirm our findings. Our study found that the increased expression of HGF in CAFs induced by MET-unamplified GC contributed to the malignant phenotype of both MET-unamplified GC and CAFs in tumor microenvironment.
登录
查看更多内容
癌症相关成纤维细胞中 microRNA-149 的表观遗传沉默介导肿瘤微环境中前列腺素 E2/白细胞介素 6 信号传导
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
16.6
作者：
Avgustinova A;Iravani M;Robertson D;Fearns A;Gao Q;Klingbeil P;Hanby AM;Speirs V;Sahai E;Calvo F;Isacke CM
通讯作者：
Isacke CM
影响因子：
82.9
作者：
Du Y;Yamaguchi H;Wei Y;Hsu JL;Wang HL;Hsu YH;Lin WC;Yu WH;Leonard PG;Lee GR 4th;Chen MK;Nakai K;Hsu MC;Chen CT;Sun Y;Wu Y;Chang WC;Huang WC;Liu CL;Chang YC;Chen CH;Park M;Jones P;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
影响因子：
50.3
作者：
Bromberg J;Wang TC
通讯作者：
Wang TC
影响因子：
10.5
作者：
Maina, F;Hilton, MC;Klein, R
通讯作者：
Klein, R