Role of β-arrestin 1 in the metastatic progression of colorectal cancer

Buchanan, F. Gregory; Gorden, D. Lee; Matta, Pranathi; Shi, Qiong; Matrisian, Lynn M.; DuBois, Raymond N.

doi:10.1073/pnas.0510562103

Cited by 246 publications

(232 citation statements)

References 26 publications

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“…However, an Akt/␤-arrestin/ protein phosphatase 2A signaling complex is also involved in dopaminergic neurotransmission (40). Moreover, prostaglandin E 2 induces the association of a prostaglandin E receptor 4/␤-arrestin 1/c-Src signaling complex, resulting in the transactivation of the EGFR and downstream Akt signaling (41). SP binding to NK-1R causes transactivation of the EGFR and MAPK phosphorylation linked to cell proliferation (9,14) and protection from colitis (15).…”

Section: Discussionmentioning

confidence: 99%

Substance P mediates antiapoptotic responses in human colonocytes by Akt activation

Koon

Zhao

Zhan

et al. 2007

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

100

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We examined the hypothesis that substance P (SP) and the neurokinin-1 receptor (NK-1R), both in vitro and in vivo, promote mucosal healing during recovery from colitis by stimulating antiapoptotic pathways in human colonic epithelial cells. For the in vitro experiments, human nontransformed NCM460 colonocytes stably transfected with NK-1R (NCM460-NK-1R cells) were exposed to SP, and cell viability assays, TUNEL assays, and Western blot analyses were used to detect apoptotic and antiapoptotic pathways. SP exposure of NCM460-NK-1R colonocytes stimulated phosphorylation of the antiapoptotic molecule Akt and inhibited tamoxifeninduced cell death and apoptosis evaluated by the cell viability assay and poly(ADP-ribose) polymerase cleavage, respectively. SP-induced phosphorylation of Akt and cleavage of poly(ADPribose) polymerase were inhibited by blockade of integrin ␣V␤3, Jak2, and activation of phosphatidylinositol 3-kinase. For the in vivo experiments, C57BL/6 mice, administered 5% dextran sulfate (DSS) dissolved in tap water for 5 days followed by a 5-day recovery period, were treated with the NK-1R antagonist CJ-12,255 or vehicle. Vehicle-treated mice showed increased colonic Akt phosphorylation and apoptosis compared with mice that received no DSS. In contrast, daily i.p. administration of CJ-12,255 for 5 days post-DSS suppressed Akt activation, exacerbated colitis, and enhanced apoptosis, and pharmacologic inhibition of Akt, either alone or together with CJ-12,255, produced a similar effect. Thus, SP, through NK-1R, possesses antiapoptotic effects in the colonic mucosa by activating Akt, which prevents apoptosis and mediates tissue recovery during colitis.apoptosis ͉ colitis

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Section: Discussionmentioning

confidence: 99%

Substance P mediates antiapoptotic responses in human colonocytes by Akt activation

Koon

Zhao

Zhan

et al. 2007

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

100

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“…For instance, β-arrestin/Ral signaling was involved in the migration and invasion of breast cancer cells induced by LPA [170] . In addition, prostaglandin E2 induced the association of prostaglandin E receptor 4 with β-arrestin 1 and c-Src, that formed a signaling complex able to induce the migration and metastasis of colorectal carcinoma cells [171] . In accordance with these data, β-arrestin 1 interacting with Src and ET A R triggered EGFR transactivation and β-catenin phosphorylation, which stimulated invasion and metastasis in ovarian cancer cells [172] .…”

Section: β-Arrestins: Novel Transducers Of Gpcr Signalsmentioning

confidence: 99%

GPCRs and cancer

Lappano

2012

Acta Pharmacol Sin

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G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.

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“…Comprehensive studies demonstrated that Src activation upon GPCR stimulation required ␤-arrestins (14,15). Recently, a new signaling mechanism, that involves the activation of ␤-arrestins in routing signals from GPCR to Src and EGFR, has been identified (16,17). Moreover, ␤-arrestin has been shown to be a necessary component in the Wnt/␤-catenin pathway by forming a complex with axin and the cytoplasmic molecule dishevelled (18,19).…”

mentioning

confidence: 99%

β-Arrestin links endothelin A receptor to β-catenin signaling to induce ovarian cancer cell invasion and metastasis

Rosanò¹,

Cianfrocca

Masi

et al. 2009

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

149

161

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The activation of endothelin-A receptor (ETAR) by endothelin-1 (ET-1) has a critical role in ovarian tumorigenesis and progression. To define the molecular mechanism in ET-1-induced tumor invasion and metastasis, we focused on ␤-arrestins as scaffold and signaling proteins of G protein-coupled receptors. Here, we demonstrate that, in ovarian cancer cells, ␤-arrestin is recruited to ETAR to form two trimeric complexes: one through the interaction with Src leading to epithelial growth factor receptor (EGFR) transactivation and ␤-catenin Tyr phosphorylation, and the second through the physical association with axin, contributing to release and inactivation of glycogen synthase kinase (GSK)-3␤ and ␤-catenin stabilization. The engagement of ␤-arrestin in these two signaling complexes concurs to activate ␤-catenin signaling pathways. We then demonstrate that silencing of both ␤-arrestin-1 and ␤-arrestin-2 inhibits ETAR-driven signaling, causing suppression of Src, mitogen-activated protein kinase (MAPK), AKT activation, as well as EGFR transactivation and a complete inhibition of ET-1-induced ␤-catenin/TCF transcriptional activity and cell invasion. ETAR blockade with the specific ETAR antagonist ZD4054 abrogates the engagement of ␤-arrestin in the interplay between ETAR and the ␤-catenin pathway in the invasive program. Finally, ETAR is expressed in 85% of human ovarian cancers and is preferentially co-expressed with ␤-arrestin-1 in the advanced tumors. In a xenograft model of ovarian metastasis, HEY cancer cells expressing ␤-arrestin-1 mutant metastasize at a reduced rate, highlighting the importance of this molecule in promoting metastases. ZD4054 treatment significantly inhibits metastases, suggesting that specific ETAR antagonists, by disabling multiple signaling activated by ETAR/␤-arrestin, may represent new therapeutic opportunities for ovarian cancer.beta-arrestin ͉ beta-catenin ͉ endothelin A receptor ͉ metastasis ͉ ovarian cancer

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Role of β-arrestin 1 in the metastatic progression of colorectal cancer

Cited by 246 publications

References 26 publications

Substance P mediates antiapoptotic responses in human colonocytes by Akt activation

Substance P mediates antiapoptotic responses in human colonocytes by Akt activation

GPCRs and cancer

β-Arrestin links endothelin A receptor to β-catenin signaling to induce ovarian cancer cell invasion and metastasis

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