Open Access

Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells

  • Authors:
    • Lingmei Li
    • Lisha Qi
    • Zhijie Liang
    • Wangzhao Song
    • Yanxue Liu
    • Yalei Wang
    • Baocun Sun
    • Bin Zhang
    • Wenfeng Cao
  • View Affiliations

  • Published online on: May 25, 2015     https://doi.org/10.3892/ijmm.2015.2222
  • Pages: 113-122
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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-β1 (TGF-β1) and epidermal growth factor (EGF). Hyaluronan (HA) has been shown to induce EMT through either TGF-β1 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-β1 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-β1 activated EGF receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we found that TGF-β1 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-β1, 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-β1 induces EMT by the transactivation of EGF signaling through HA/CD44 in lung and breast cancer cells.
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July-2015
Volume 36 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li L, Qi L, Liang Z, Song W, Liu Y, Wang Y, Sun B, Zhang B and Cao W: Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells. Int J Mol Med 36: 113-122, 2015.
APA
Li, L., Qi, L., Liang, Z., Song, W., Liu, Y., Wang, Y. ... Cao, W. (2015). Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells. International Journal of Molecular Medicine, 36, 113-122. https://doi.org/10.3892/ijmm.2015.2222
MLA
Li, L., Qi, L., Liang, Z., Song, W., Liu, Y., Wang, Y., Sun, B., Zhang, B., Cao, W."Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells". International Journal of Molecular Medicine 36.1 (2015): 113-122.
Chicago
Li, L., Qi, L., Liang, Z., Song, W., Liu, Y., Wang, Y., Sun, B., Zhang, B., Cao, W."Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells". International Journal of Molecular Medicine 36, no. 1 (2015): 113-122. https://doi.org/10.3892/ijmm.2015.2222