The multiple roles of amphiregulin in human cancer

Busser, Benoît; Sancey, Lucie; Brambilla, Élisabeth; Coll, Jean‐Luc; Hurbin, Amandine

doi:10.1016/j.bbcan.2011.05.003

Cited by 168 publications

(200 citation statements)

References 173 publications

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“…Accumulating lines of evidence show that AREG is transported to the plasma membrane and is secreted to act as a ligand for EGFR (16). However, recent study demonstrated that intracellular AREG translocates to the inner nuclear envelope and then regulates chromatin remodeling (7).…”

Section: Resultsmentioning

confidence: 99%

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Taira

Yamaguchi

Kimura

et al. 2013

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

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Upon DNA damage, tumor suppressor p53 determines cell fate by repairing DNA lesions to survive or by inducing apoptosis to eliminate damaged cells. The decision is based on its posttranslational modifications. Especially, p53 phosphorylation at Ser46 exerts apoptotic cell death. However, little is known about the precise mechanism of p53 phosphorylation on the induction of apoptosis. Here, we show that amphiregulin (AREG) is identified for a direct target of Ser46 phosphorylation via the comprehensive expression analyses. Ser46-phosphorylated p53 selectively binds to the promoter region of AREG gene, indicating that the p53 modification changes target genes by altering its binding affinity to the promoter. Although AREG belongs to a family of the epidermal growth factor, it also emerges in the nucleus under DNA damage. To clarify nuclear function of AREG, we analyze AREG-binding proteins by mass spectrometry. AREG interacts with DEAD-box RNA helicase p68 (DDX5). Intriguingly, AREG regulates precursor microRNA processing (i.e., miR-15a) with DDX5 to reduce the expression of antiapoptotic protein Bcl-2. These findings collectively support a mechanism in which the induction of AREG by Ser46-phosphorylated p53 is required for the microRNA biogenesis in the apoptotic response to DNA damage. microarray | Drosha | miRNA processing

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Section: Resultsmentioning

confidence: 99%

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Taira

Yamaguchi

Kimura

et al. 2013

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

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“…Notably, the contributions of AREG and EREG as pro-oncogenic factors in pancreatic cancer have previously been established (22,50). Signaling from AREG, specifically autocrine secretion, has been implicated in chemoresistance, evasion of apoptosis, self-sufficiency in growth signals, proliferation, angiogenesis, invasion, and metastasis (20). In fact, AREG secretion levels in pancreatic cancer patients are elevated to the point that this ligand has been identified as a potential biomarker that is associated with a worse outcome (51).…”

Section: Discussionmentioning

confidence: 99%

“…This release creates feedback loops in primary and metastatic sites to promote tumor progression. AREG may also enter the bloodstream and travel to distant organs, acting as an endocrine signal (20), and thus potentially creating a favorable microenvironment (21). This property allows tumors to maintain a high rate of proliferation with a reduced requirement for exogenously supplied growth factors (13).…”

mentioning

confidence: 99%

Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF)

Carpenter

Chen

Knifley

et al. 2015

Journal of Biological Chemistry

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Background: Integrin ␣6␤4 is overexpressed in pancreatic cancer and enhances invasion. Results: Integrin ␣6␤4 coordinately up-regulates AREG, EREG, and MMP1 through DNA demethylation and NFAT5 that in turn enhances HGF-mediated invasion. Conclusion: Integrin ␣6␤4 stimulates HGF-dependent invasion through autocrine EGFR signaling. Significance: HGF-stimulated invasion is dependent on autocrine EGFR signaling, thus implicating why EGFR inhibitors are effective in a complex tumor microenvironment.

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“…2E). Finally, since AREG is an EGFR ligand, 32,33 we asked whether the EGFR signaling pathway was indeed activated by TAZ. Immunoblot revealed an increase of phospho-EGFR as well as the activation of down stream PI3K/ AKT and MAPK pathways by wt-and mutant TAZ (Fig.…”

Section: Tazmentioning

confidence: 99%

TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin

et al. 2012

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The multiple roles of amphiregulin in human cancer

Cited by 168 publications

References 173 publications

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage

Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF)

TAZ induces growth factor-independent proliferation through activation of EGFR ligand amphiregulin

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