Angiotensin II and epidermal growth factor receptor cross‐talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines

Itabashi, Hideyuki; Maesawa, Chihaya; Oikawa, Hiroki; Kotani, Koji; Sakurai, Eiichi; Kato, Kuniyuki; Komatsu, Hideaki; Nitta, Hiroyuki; Kawamura, Hidenobu; Wakabayashi, Go; Masuda, Tomoyuki

doi:10.1111/j.1872-034x.2007.00304.x

Cited by 42 publications

(34 citation statements)

References 45 publications

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“…HB-EGF binds and activates intracellular signaling cascades downstream of EGFR, such as the AKT pathway, and thereby promotes the growth of normal and neoplastic cells (25,26). In our study, we found that the EGFR-AKT pathway was involved in the suppressive action of miR-126/ADAM9 in ESCC.…”

Section: Overexpression Of Mir-126 Suppresses Escc Cell Proliferationmentioning

confidence: 49%

“…In addition, we investigated the downstream pathway and found that ADAM9 was critical for promoting cell proliferation in ESCC by targeting EGFR-AKT signaling. ADAM9 cleaved the pro-HB-EGF precursor to yield soluble HB-EGF, which binds to EGFR, thereby activating downstream signal transduction (26,41). The EGFR-AKT pathway is important for cell growth and migration (42,43).…”

Section: Discussionmentioning

confidence: 99%

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DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

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Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)-based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)-specific miRNAs and miRNArelated epigenetic modulations.Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor-AKT signaling.Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel "DNMT1-miR-126 epigenetic circuit" is involved in ESCC progression. Consequently, miR-126-based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics.

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Section: Overexpression Of Mir-126 Suppresses Escc Cell Proliferationmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

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“…Although they all overexpress EGFR, the expression level is greater in PC-9 than in either of the wild type cell lines, A549 or H460 (Okabe et al, 2007). Moreover, we explored the anti-proliferative activity of CIU1 on the EGFR-low liver cancer cell line and the EGFR-high colorectal cell line HepG2 (Itabashi et al, 2008) and HT29 (Matsuo et al, 2011), respectively. The number of viable cancer cells after 24 h treatment of CIU1 was evaluated using the WST-1 (a water-soluble tetrazolium salt, (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt) colorimetric assay.…”

Section: Sensitivity Over a Panel Of Solid Tumor Cell Linesmentioning

confidence: 98%

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

Mudjupa

Abdelhamed

Refaat

et al. 2015

JAB

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Available online xxxKeywords: Caffeic acid derivatives EGFR inhibitor Triple-negative breast cancer Non-small cell lung cancer Molecular modeling Abbreviations: CA, caffeic acid CAPE, caffeic acid phenethyl ester EGFR, epidermal growth factor receptor RTK, receptor tyrosine kinase TNBC, triple-negative breast cancer a b s t r a c t A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido) vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type nonsmall-cell lung cancer H460 cells with IC 50 values of 8.96 mM and 12.98 mM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC 50 2.34 mM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

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“…60 ADAM17 also influences tumour cell proliferation when over-expressed in cancers such as breast, 61 ovary, 62 kidney, 63 colon, 64 prostate 65 and primary hepatocellular carcinomas. 66 A mechanism proposed by Itabashi et al 66 suggested that this increased cellular proliferation is mediated by ADAM proteins, particularly ADAM17, via EGFR signal transactivation triggered by angiotensin II (Ang II) stimulation. The direct stimulation of EGFR by ligand binding results in the dimerisation and subsequent phosphorylation of the two receptor molecules.…”

Section: Adams and Cancermentioning

confidence: 99%

“…67 Ang II acts as a potent growth factor of vascular smooth muscle cells and certain cancer cell lines in addition to its fundamental role as a vasoconstrictor controlling cardiovascular function and renal homeostasis. 66 Similarly, amphiregulin (a ligand of EGFR) is released by ADAM17 68 and enhances proliferation of cancer cells. 20…”

Section: Adams and Cancermentioning

confidence: 99%

ADAMs and ADAMTSs in cancer

Turner

Blair-Zajdel²,

Bunning³

2009

British Journal of Biomedical Science

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ADAMs and ADAMTSs are multi-domain proteins characterised by the presence of both metalloproteinase and disintegrin-like domains. ADAM proteins are usually type 1 transmembrane proteins, and ADAMTSs are secreted from cells. The dysregulated expression of ADAMs and ADAMTSs has been reported in a wide range of human cancers, where, in many cases, they are implicated as positive regulators of cancer progression. Proteolytically active ADAMs act as ectodomain sheddases, which release extracellular regions of membrane-bound proteins (e.g., adhesion molecules, growth factors, cytokines, chemokines and receptors). Certain ADAMTSs break down extracellular matrix (ECM) proteoglycans (e.g., aggrecan, brevican and versican). Through these actions they are able to sculpt the tumour microenvironment and modulate key processes involved in cancer progression, including cell proliferation, migration and angiogenesis. Members of both groups of protein can also act to inhibit or slow cancer progression: ADAMs can interact with specific integrins to elicit inhibitory effects on cancer dissemination, and certain ADAMTSs possess antiangiogenic activity, which prevents an increase in tumour size. This review covers recent developments in the involvement of ADAM and ADAMTS proteins in human cancer.

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Angiotensin II and epidermal growth factor receptor cross‐talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines

Abstract: These results suggest that AngII-EGFR cross-talk signaling mediated by ADAMs is involved in the proliferation and invasion activities of several HCC cell lines.

Cited by 42 publications

References 45 publications

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

ADAMs and ADAMTSs in cancer

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