期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 36, 期 1, 页码 113-122出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2015.2222
关键词
epithelial-mesenchymal transition; transforming growth factor-1; hyaluronan; CD44; epidermal growth factor
资金
- National Natural Science Foundation of China [81001186, 81201725, 81402420]
- Tianjin Municipal Science and the Technology Commission [10JCYBJC14100, 13JCYBJC21800, 15JCQNJC12400]
Epithelial-mesenchymal transition (EMT), a process closely related to tumor development, is regulated by a variety of signaling pathways and growth factors, such as transforming growth factor-1 (TGF-1) and epidermal growth factor (EGF). Hyaluronan (HA) has been shown to induce EMT through either TGF-1 or EGF signaling and to be a regulator of the crosstalk between these two pathways in fibroblasts. In this study, in order to clarify whether HA has the same effect in tumor cells, we utilized the lung cancer cell line, A549, and the breast cancer cell line, MCF-7, and found that the effects of stimulation with TGF-1 were more potent than those of EGF in regulating the expression of EMT-associated proteins and in enhancing cell migration and invasion. In addition, we observed that TGF-1 activated EGF receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we found that TGF-1 upregulated the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and promoted the expression of CD44, a cell surface receptor for HA, which interacts with EGFR, resulting in the activation of the downstream AKT and ERK pathways. Conversely, treatment with 4-methylumbelliferone (4-MU; an inhibitor of HAS) prior to stimulation with TGF-1, inhibited the expression of CD44 and EGFR, abolished the interaction between CD44 and EGFR. Furthermore, the use of shRNA targeting CD44 impaired the expression of EGFR, deactivated the AKT and ERK pathways, reversed EMT and decreased the migration and invasion ability of cells. In conclusion, our data demonstrate that TGF-1 induces EMT by the transactivation of EGF signaling through HA/CD44 in lung and breast cancer cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据