FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma

Qi, Lisha; Song, Wangzhao; Li, Lingmei; Cao, Lu; Yu, Yue; Song, Chao; Wang, Yalei; Zhang, Fei; Li, Yang; Zhang, Bin; Cao, Weijun

doi:10.18632/oncotarget.12187

Cited by 46 publications

(33 citation statements)

References 42 publications

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“…FGF/FGFR signaling has been reported to be involved in hepatocarcinogenesis [19][20][21]. Among FGFRs 1-4, the most frequently expressed in clinical HCC samples is FGFR4, the ligand of which is FGF19 [19].…”

Section: Discussionmentioning

confidence: 99%

“…Among them, FGFR4 expression has been observed most frequently in HCC tissues [19]; the ligand of FGFR4 is FGF19. In other studies, elevated serum FGF19 levels were seen in HCC patients [20] and high levels of FGF19 and FGFR4 were associated with poor outcomes in HCC patients [21]. Elevation of FGF23 levels have been shown to be a surrogate marker of FGFR1 inhibition [22], and in particular, circulating FGF23 levels were increased by Lenvatinib therapy in thyroid cancer [23].…”

Section: Introductionmentioning

confidence: 90%

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Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma

Chuma

Uojima

Numata

et al. 2020

Cancers

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Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma

Chuma

Uojima

Numata

et al. 2020

Cancers

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“…More importantly, FGF4 induces EMT via enhancement of store-operated calcium entry in lung ADC cells. 33 CD44 was identified as one of the many genes that ESRP1 targets for alternative splicing. This cell surface protein is a major marker for stem-like cancer cells and has been implicated in a variety of physiologic processes in addition to cancer cell invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Epithelial Splicing Regulatory Protein 1 Inhibits the Invasion and Metastasis of Lung Adenocarcinoma

et al. 2018

The American Journal of Pathology

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Despite the development of various treatments, metastasis remains a significant problem with lung adenocarcinoma (ADC). The role and mechanism of epithelial splicing regulatory protein 1 (ESRP1), an epithelial-specific RNA binding protein, on promoting the invasion and metastasis of lung ADC remain to be fully elucidated. Immunohistochemical analysis in 125 human lung ADC tissue samples demonstrated that ESRP1 overexpression was inversely related to the presence of metastases, tumor size, and clinical stage of lung ADC. Impaired ESRP1 expression was also found to stimulate the invasion capacity of lung ADC cells both in vitro and in vivo. Functionally, overexpression of the ZEB1 gene decreased ESRP1 expression, and knockdown of the ZEB1 gene caused increased ESRP1 expression. On the basis of a gene array analysis, the expression of ESRP1 was associated with the regulation of the extracellular matrix. The expression of CD44 and fibroblast growth factor receptor, representatives that interact with the extracellular matrix, was studied. The CD44 subtypes promoted lung ADC cell invasion by regulating matrix metalloproteinase 2 expression. In conclusion, ESRP1 inhibits the invasion and metastasis of lung ADC and plays a role in regulating proteins involved in epithelial-to-mesenchymal transition.

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“…However, the mechanism of bFGF in bleomycin-induced EMT is not clear. The PI3K/Akt pathway can be activated by bFGF and plays an important role in lung fibrosis and EMT [31,32]. Thus, we investigated the effects of bFGF-activated PI3K/Akt signaling in bleomycin-induced EMT.…”

Section: Bleomycin Induced Emt Partly Through Bfgf/pi3k/akt/esrp1 Sigmentioning

confidence: 99%

Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis

Weng

Chen

et al. 2020

Bioscience Reports

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Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial-mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-β1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-β1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-β1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.

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FGF4 induces epithelial-mesenchymal transition by inducing store-operated calcium entry in lung adenocarcinoma

Cited by 46 publications

References 42 publications

Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma

Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma

Epithelial Splicing Regulatory Protein 1 Inhibits the Invasion and Metastasis of Lung Adenocarcinoma

Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis

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