C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis

Chen, Zhuo; Tong, Linjiang; Tang, Baiyou; Liu, Hongyan; Wang, Xin; Zhang, Tao; Cao, Xianwen; Chen, Yi; Li, Honglin; Qian, Xuhong; Xu, Yufang; Xie, Hua; Ding, Jian

doi:10.1038/s41401-018-0191-7

Cited by 20 publications

(9 citation statements)

References 46 publications

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“…The inhibitory activity of compounds on growth was evaluated using the sulforhodamine B (SRB) colorimetric assay. Cells were seeded in 96-well plates, cultured overnight, and treated with a dilution series of test compounds for 72 h. Then, the SRB assay was performed according to standard protocols, as described previously [40].…”

Section: In Vitro Cell Proliferation Assaysmentioning

confidence: 99%

Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance

Zhang

Chan³

et al. 2020

Mol Cancer

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Background: Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond to first-generation EGFR inhibitors; however, the efficacy of these drugs is limited by acquired resistance driven by the EGFR T790M mutation. The discovery of third-generation EGFR inhibitors overcoming EGFR T790M and their new resistance mechanisms have attracted much attention. Methods: We examined the antitumor activities and potential resistance mechanism of a novel EGFR thirdgeneration inhibitor in vitro and in vivo using ELISA, SRB assay, immunoblotting, flow cytometric analysis, kinase array, qRT-PCR and tumor xenograft models. The clinical effect on a patient was evaluated by computed tomography scan. Results: We identified compound ASK120067 as a novel inhibitor of EGFR T790M , with selectivity over EGFR WT. ASK120067 exhibited potent anti-proliferation activity in tumor cells harboring EGFR T790M (NCI-H1975) and sensitizing mutations (PC-9 and HCC827) while showed moderate or weak inhibition in cells expressing EGFR WT. Oral administration of ASK120067 induced tumor regression in NSCLC xenograft models and in a PDX model harboring EGFR T790M. The treatment of one patient with advanced EGFR T790M-positive NSCLC was described as proof of principle. Moreover, we found that hyperphosphorylation of Ack1 and the subsequent activation of antiapoptotic signaling via the AKT pathway contributed to ASK120067 resistance. Concomitant targeting of EGFR and Ack1 effectively overrode the acquired resistance of ASK120067 both in vitro and in vivo. Conclusions: Our results idenfity ASK120067 as a promising third-generation EGFR inhibitor and reveal for the first time that Ack1 activation as a novel resistance mechanism to EGFR inhibitors that guide to potential combination strategy.

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Section: In Vitro Cell Proliferation Assaysmentioning

confidence: 99%

Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance

Zhang

Chan³

et al. 2020

Mol Cancer

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“…17,18 C11, an inhibitor of FGFR1, could curb angiogenesis and metastasis of BC. 34 Previous research revealed that FGFR1 promoted resistance to endocrine therapy and acted as a possible target for BC. 35 One report uncovered that FGFR1 expression was inhibited by miR-361-5p, which impeded BC cell invasion, proliferation, and glycolysis.…”

Section: Discussionmentioning

confidence: 99%

“…FGFR1 has been demonstrated as an oncogene in a series of cancers 17, 18 . C11, an inhibitor of FGFR1, could curb angiogenesis and metastasis of BC 34 . Previous research revealed that FGFR1 promoted resistance to endocrine therapy and acted as a possible target for BC 35 .…”

Section: Discussionmentioning

confidence: 99%

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR‐326/FGFR1 axis

et al. 2020

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Background Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)‐326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR‐326 was verified by dual‐luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay. Results Circ_0000518 and FGFR1 were upregulated while miR‐326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR‐326 in BC cells. MiR‐326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR‐326 mimic‐mediated influence on the malignant behaviors of BC cells. Conclusions Circ_0000518 facilitated BC development via regulation of the miR‐326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.

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“…Finally, our findings strongly identified that by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway, MFA attenuated the ability of migration and proliferation, attenuated the expression of fibrosis-related proteins in HCFs, and improved the cardiac function in MI mice meanwhile. But interestingly, we found that when mice injected by MFA without MI, the expression of α-SMA was significantly decreased, from other reports we knew that ferulic acid (FA), the ramification of MFA, suppressed the expression of fibroblast growth factor receptor 1 (FGFR1), and hence suppressed the angiogenesis and α-SMA expression (Yang et al, 2015;Chen et al, 2019). Although the effect of MFA on FGFR1 was not reported, we assumed that it might play the same role as FA.…”

Section: Discussionmentioning

confidence: 80%

Methyl Ferulic Acid Attenuates Human Cardiac Fibroblasts Differentiation and Myocardial Fibrosis by Suppressing pRB-E2F1/CCNE2 and RhoA/ROCK2 Pathway

Liao

Qi²,

Tang

et al. 2021

Front. Pharmacol.

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Background: Myocardial fibrosis is a key pathological process after myocardial infarction, which leads to poor outcomes in patients at the end stage. Effective treatments for improving prognosis of myocardial fibrosis are needed to be further developed. Methyl ferulic acid (MFA), a biologically active monomer extracted and purified from the Chinese herbal medicine, is reported as an attenuator in many diseases. In this study, we aim to reveal the role it plays in myocardial fibrosis after myocardial infarction and its possible mechanism.Results: Firstly, we found that MFA attenuated the expression of fibrosis-related proteins and the ability of migration and proliferation in TGF-β1–induced human cardiac fibroblasts (HCFs). Then, myocardial fibrosis after myocardial infarction models on mouse was built to reveal the in vivo affection of MFA. After 28 days of treatments, fibrosis areas, cardiac function, and expression of fibrosis-related proteins were all improved in the MFA-treated group than the myocardial infarction group. Finally, to elucidate the mechanism of phenomenon we observed, we found that MFA attenuated HCF differentiation after myocardial infarction by suppressing the migration and proliferation in HCFs, which was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.Conclusion: Our findings showed that MFA attenuated the expression of fibrosis-related proteins, and the ability of migration and proliferation in HCFs improved the cardiac function of myocardial infarction mice; meanwhile, the mechanism of that was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.

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C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis

Cited by 20 publications

References 46 publications

Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance

Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance

Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR‐326/FGFR1 axis

Methyl Ferulic Acid Attenuates Human Cardiac Fibroblasts Differentiation and Myocardial Fibrosis by Suppressing pRB-E2F1/CCNE2 and RhoA/ROCK2 Pathway

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