Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

Berndt, Alexander; Büttner, R.; Gühne, Stefanie; Gleinig, Anna; Richter, Petra; Chen, Yuan; Franz, Marcus; Liebmann, Claus

doi:10.1016/j.yexcr.2013.12.024

Cited by 15 publications

(16 citation statements)

References 51 publications

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“…We then separately investigated the activation of pathways following exposure to TGF-β1 or EGF for 4 h. Our data demonstrated that TGF-β1 not only induced the activation of the Smad pathway, but also induced the phosphorylation of AKT and ERK ( Fig. 1C ), which are commonly considered to be downstream molecules of the EGF/EGFR pathway ( 13 ).…”

Section: Resultsmentioning

confidence: 88%

“…Epidermal growth factor (EGF) has been shown to disrupt cell-cell junctions and induce EMT in a number of cell lines ( 10 – 12 ). EGF stimulates signaling pathways through the EGF receptor (EGFR), which is associated with a more invasive behavior and a poor prognosis ( 13 , 14 ). TGF-β1 and EGF have been implicated in the process of EMT, and their corresponding intracellular transduction pathways have been reported to form highly interconnected networks; however, the mechanisms involved has not been determined yet ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

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

Liang

et al. 2015

International Journal of Molecular Medicine

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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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Section: Resultsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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

Liang

et al. 2015

International Journal of Molecular Medicine

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“…Mitogenic signaling is the most common molecular and genetic alteration which characterizes OSCC and is primarily mediated by the PI3K/Akt/MTOR pathway . Consequently, the relationship between OSCC and the PI3K pathway has been of substantial interest . PI3K/Akt/mTOR pathway activation may be elicited by somatic mutations, and stimulated epidermal growth factor receptor (EGFR), insulin‐like growth factor receptor (ILGFR), or G protein‐coupled receptors.…”

Section: The Pi3k/akt/mtor Pathway and Oral Carcinogenesismentioning

confidence: 99%

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Sonis

Mendes

2016

J Oral Pathology Medicine

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The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders.

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“…[234][235][236][237] Myofibroblasts and cancerassociated fibroblasts have been shown to enhance HNSCC invasion in vitro in a variety of assays. [238][239][240][241][242][243][244][245][246][247] Treatments that can enhance the ability of fibroblasts to stimulate tumor cell invasion include irradiation 182 and reactive oxygen species, 183,248,249 as well as lifestyle-correlated factors, such as cigarette smoke 250 and areca nut extract. 251 Fibroblasts have been shown to stimulate tumor cell invasion through secretion of a number of factors, including chemokine (C-C motif) ligand 2 (CCL2), 183,252 260 and hepatocyte growth factor (HGF).…”

Section: Tumor Microenvironment and Invasionmentioning

confidence: 99%

Mechanisms of Invasion in Head and Neck Cancer

Jimenez¹,

Jayakar²,

Ow³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The highly invasive properties demonstrated by head and neck squamous cell carcinoma (HNSCC) are often associated with locoregional recurrence and lymph node metastasis in patients and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed.Objectives.-To provide an overview of the characteristics, mediators, and mechanisms of HNSCC invasion.Data Sources.-A literature review of peer-reviewed articles in PubMed on HNSCC invasion.Conclusions.-Histologic features of HNSCC tumors can help predict prognosis and influence clinical treatment decisions. Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.

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Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

Cited by 15 publications

References 51 publications

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

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

Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Mechanisms of Invasion in Head and Neck Cancer

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