Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells

Civenni, Gianluca; Holbro, Thomas; Hynes, Nancy E.

doi:10.1038/sj.embor.embor735

Cited by 122 publications

(102 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With this report and previous studies describing transactivation of receptor tyrosine kinases by Wnt protein, (50)(51)(52) it seems that the network of signaling pathways activated by Wnt proteins is becoming more complex, especially when a Wnt protein activates several tyrosine kinase receptors in a particular cell type.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 57%

“…The PKC inhibitor, GO6983, also did not influence the transactivation of PDGF-Rs by Wnt3a, suggesting that it probably acts downstream of PLCg activation by PDGF-Rs. To our knowledge, this is the first report on transactivation of PDGF-Rs by a Wnt protein, whereas transactivation of EGF-Rs has already been reported in mammary epithelial cells, (52) NIH3T3 cells, (50) and breast cancer cells. (51) The molecular mechanism by which Wnt proteins transactivate some receptor tyrosine kinases remains poorly understood.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 71%

See 1 more Smart Citation

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Previous studies have shown that Wnt3a enhances the proliferation and inhibits the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, we investigated the signaling pathways involved in Wnt3a-induced osteoblastic cell proliferation. Experiments with DKK1, a natural antagonist of Lrp5/6, indicated that Wnt/b-catenin did not play a major role in Wnt3a-induced osteoblastic cell proliferation. The use of selective inhibitors of known mitogenic pathways implicates Src family kinases (SFKs) and a protein kinase C (PKC) in this cellular response. Time-dependent analysis of signaling molecules activated by Wnt3a in MC3T3-E1 cells revealed parallel activation of the canonical pathway and of several tyrosine kinases, including SFKs and PDGF receptors (PDGF-Rs). Functional analysis with specific inhibitors suggested a major role of PDGF-Rs in mediating Wnt3a-induced cell proliferation. Further investigation with an si-RNA approach confirmed a predominant role of this receptor in this cellular response. The use of soluble decoy PDGF-Rs that can sequester extracellular PDGFs excluding that part of the increased PDGF receptor phosphorylation by Wnt3a was the result of autocrine production of PDGFs. A selective SFK inhibitor blunted the enhanced PDGF-R phosphorylation and cell proliferation induced by Wnt3a. Studies of initial events involved in the regulation of this pathway suggest a role of dishevelled. In conclusion, data presented in this study indicate that cell proliferation induced by Wnt3a in osteoblastic cells is mediated by a dishevelleddependent and b-catenin-independent pathway, which involves the transactivation of PDGF receptors. ß

show abstract

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 57%

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 71%

Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation

Caverzasio

Thouverey

2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Fold of elevation was determined (n ϭ 5 controls; n ϭ 5 mutants). * , P Ͻ 0.05; *** , P Ͻ 0.005. activation, including the pathway involving GPCR-mediated release of soluble ligands for EGFR (22,23).…”

Section: Resultsmentioning

confidence: 99%

erbB2 is required for G protein-coupled receptor signaling in the heart

Negro

Brar

et al. 2006

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

View full text Add to dashboard Cite

erbB2͞Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian development and human disease. The absence of erbB2 signaling in cardiac myocytes results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects observed in a subset of breast cancer patients treated with the anti-Her2 antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for integrating signaling networks involving multiple classes of extracellular signals. However, its role in G protein-coupled receptor (GPCR) signaling remains undefined. Because the activation of the MAPK pathway through GPCR signaling is important for cardiac homeostasis, we investigated whether erbB2 is required for GPCR-mediated MAPK signaling in wild-type and heart-specific erbB2 mutant mice. Here we demonstrate that erbB2, but not EGF receptor, is essential for MAPK activation induced by multiple GPCR agonists in cardiac myocytes. erbB2 is immunocomplexed with a GPCR in vivo and is transactivated after ligand treatment in vitro. Coexpression of erbB2 with GPCRs in heterologous cells results in ligand-dependent complex formation and MAPK activation. Furthermore, MAPK activation and cardiac contractility are markedly impaired in heart-specific erbB2 mutants infused with a GPCR agonist. These results reveal an essential mechanism requiring erbB2 as a coreceptor for GPCR signaling in the heart. The obligatory role of erbB2 in GPCR-dependent signaling may also be important in other cellular systems.MAPK ͉ cardiac myocytes ͉ erbB2 mutants

show abstract

“…breast cancer cells; Civenni et al, 2003;Musgrove, 2004). Recently published data on transgenic mice overexpressing b-catenin strengthen this assumption, as increased b-catenin expression leads to elevated EGFR levels in hepatocytes.…”

Section: Cross-talk With Protumorigenic Factorsmentioning

confidence: 97%