The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells

Tanida, Satoshi; Joh, Takashi; Itoh, K.; Kataoka, Hiromi; Sasaki, Makoto; Ohara, Hirotaka; Nakazawa, Takahiro; Nomura, Tomoyuki; Kinugasa, Yumi; Ohmoto, Hiroshi; Ishiguro, Hiroshi; Yoshino, Kohichiro; Higashiyama, Shigeki; Itoh, Makoto

doi:10.1053/j.gastro.2004.05.017

Cited by 89 publications

(78 citation statements)

References 43 publications

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“…Therefore, the mechanisms of TNF-regulated antiapoptotic responses are important in understanding the role of TNF in the pathogenesis of inflammation and inf lammation-associated tumorigenesis. Activation of EGFR and other ErbB family members by cytokines has been reported in several cell types (13)(14)(15)(16). TNF stimulates rapid EGFR phosphorylation on Tyr-1068 in HeLa cells, although at a lower level of phosphorylation than with EGF treatment (28), consistent with our finding that EGF is more effective than TNF in stimulating increased EGFR phosphorylation in YAMC cells (Figs.…”

Section: Fig 4 Suppression Of Egfr and Erbb2 Expression Promotes Apsupporting

confidence: 91%

“…In addition, EGFR can be transactivated by various extracellular stimuli, such as agonists for G protein-coupled receptors (GPCR) and cytokine receptors (12). TNF, IL-8, IL-1␣, IL-1␤, and IFN-␥ have been reported to transactivate EGFR in hepatocytes (13), mammary epithelial cells (14), and cancer-derived cell lines (15,16). Members of the Src family of nonreceptor intracellular tyrosine kinases have been implicated as targets of GPCRs in EGFR transactivation via direct phosphorylation of cytoplasmic domains of EGFR or via stimulation of matrix metalloproteinase (MMP) activity to promote the release of the membrane-bound EGFR ligand (17,18).…”

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confidence: 99%

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Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis

Yamaoka¹,

Yan²,

Cao³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

100

114

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TNF is a pleiotropic cytokine that activates both anti-and proapoptotic signaling pathways, with cell fate determined by the balance between these two pathways. Activation of ErbB family members, including EGF receptor (EGFR/ErbB1), promotes cell survival and regulates several signals that overlap with those stimulated by TNF. This study was undertaken to determine the effects of TNF on EGFR and ErbB2 activation and intestinal epithelial cell survival. Mice, young adult mouse colon epithelial cells, and EGFR knockout mouse colon epithelial cells were treated with TNF. Activation of EGFR, ErbB2, Akt, Src, and apoptosis were determined in vivo and in vitro. TNF stimulated EGFR phosphorylation in young adult mouse colon epithelial cells, and loss of EGFR expression or inhibition of kinase activity increased TNF-induced apoptosis, which was prevented in WT but not by kinase-inactive EGFR expression. Similarly, TNF injection stimulated apoptosis in EGFR-kinasedefective mice (EGFR wa2 ) compared with WT mice. TNF also activated ErbB2, and loss of ErbB2 expression increased TNF-induced apoptosis. Furthermore, Src-kinase activity and the expression of both EGFR and ErbB2 were required for TNF-induced cell survival. Akt was shown to be a downstream target of TNF-activated EGFR and ErbB2. These findings demonstrate that EGFR and ErbB2 are critical mediators of TNF-regulated antiapoptotic signals in intestinal epithelial cells. Given evidence for TNF signaling in the development of colitis-associated carcinoma, this observation has significant implications for understanding the role of EGFR in maintaining intestinal epithelial cell homeostasis during cytokinemediated inflammatory responses.

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Section: Fig 4 Suppression Of Egfr and Erbb2 Expression Promotes Apsupporting

confidence: 91%

mentioning

confidence: 99%

Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis

Yamaoka¹,

Yan²,

Cao³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

100

114

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“…IL-8-mediated EGFR transactivation has also been previously reported in SK-OV-3 human ovarian cancer cells and human microvascular endothelial cells following stimulation by IL-8 (38). Studies by Tanida et al (39) have demonstrated IL-8-mediated EGFR transactivation also occurs in KATO III gastric epithelial cells. Moreover, these investigators found that this activity was dependent on the metalloproteinase ADAM-10.…”

Section: Discussionmentioning

confidence: 66%

Macrophage-Inflammatory Protein-3α Mediates Epidermal Growth Factor Receptor Transactivation and ERK1/2 MAPK Signaling in Caco-2 Colonic Epithelial Cells via Metalloproteinase-Dependent Release of Amphiregulin

Keates

Han

Kelly

et al. 2007

The Journal of Immunology

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Previously, we reported that normal colonocytes produce the memory CD4+ T cell-directed chemokine MIP-3α, and that epithelial MIP-3α levels are elevated in inflammatory bowel disease. Interestingly, the unique receptor for MIP-3α, CCR6, is expressed by a variety of cell types including colonocytes, suggesting that MIP-3α may regulate additional biological activities in the intestine. The aim of this study was to determine whether MIP-3α can induce intestinal epithelial cell proliferation and to examine the signaling mechanisms that mediate this response. We show that nonstimulated Caco-2 and HT-29 colonic epithelial cells express CCR6, and that stimulation of Caco-2 cells by MIP-3α can dose dependently increase cell proliferation as well as activate the epidermal growth factor receptor (EGFR) and ERK1/2 MAPK. MIP-3α-mediated ERK1/2 activation in Caco-2 cells appeared to require metalloproteinase-dependent release of the endogenous EGFR ligand amphiregulin and transactivation of the EGFR. Moreover, blockade of amphiregulin bioactivity using a neutralizing polyclonal Ab significantly reduced MIP-3α-mediated, but not EGF-mediated Caco-2 cell proliferation. Taken together, our findings indicate that MIP-3α can regulate mitogenic signaling in colonic epithelial cells and thus may serve an important homeostatic function in the intestine by regulating tissue turnover and maintenance of the epithelium, in addition to its role in regulating leukocyte recruitment.

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“…Recent studies including our own have shown that exposure to anticancer drugs or ionizing radiation can activate stress pathways, which trigger activation of multiple signaling pathways, such as those regulated by the human epidermal receptor (HER) tyrosine kinase family (1)(2)(3)(4)(5).…”

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confidence: 99%

Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer

Kyula

Schaeybroeck

Doherty

et al. 2010

Clinical Cancer Research

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Purpose: We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined the role of ADAMs (a disintegrin and metalloproteinases) and soluble growth factors in this acute drug resistance mechanism.Experimental Design: In vitro and in vivo models of CRC were assessed. ADAM-17 activity was measured using a fluorometric assay. Ligand shedding was assessed by ELISA or Western blotting. Apoptosis was assessed by flow cytometry and Western blotting.Results: Chemotherapy (5-fluorouracil) treatment resulted in acute increases in transforming growth factor-α, amphiregulin, and heregulin ligand shedding in vitro and in vivo that correlated with significantly increased ADAM-17 activity. Small interfering RNA-mediated silencing and pharmacologic inhibition confirmed that ADAM-17 was the principal ADAM involved in this prosurvival response. Furthermore, overexpression of ADAM-17 significantly decreased the effect of chemotherapy on tumor growth and apoptosis. Mechanistically, we found that ADAM-17 not only regulated phosphorylation of human epidermal receptors but also increased the activity of a number of other growth factor receptors, such as insulin-like growth factor-I receptor and vascular endothelial growth factor receptor.Conclusions: Chemotherapy acutely activates ADAM-17, which results in growth factor shedding, growth factor receptor activation, and drug resistance in CRC tumors. Thus, pharmacologic inhibition of ADAM-17 in conjunction with chemotherapy may have therapeutic potential for the treatment of CRC. Clin Cancer Res; 16(13); 3378-89. ©2010 AACR.

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The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells

Cited by 89 publications

References 43 publications

Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis

Transactivation of EGF receptor and ErbB2 protects intestinal epithelial cells from TNF-induced apoptosis

Macrophage-Inflammatory Protein-3α Mediates Epidermal Growth Factor Receptor Transactivation and ERK1/2 MAPK Signaling in Caco-2 Colonic Epithelial Cells via Metalloproteinase-Dependent Release of Amphiregulin

Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer

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