ABI3, a component of the WAVE2 complex, is potentially regulated by PI3K/AKT pathway

ABI3, a component of the WAVE2 complex, is potentially regulated by PI3K/AKT pathway

Author Moraes, Lais Autor UNIFESP Google Scholar
Zanchin, Nilson I. T. Google Scholar
Cerutti, Janete M. Autor UNIFESP Google Scholar
Abstract We previously reported that ABI3 expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth in vivo. The mechanistic basis by which ABI3 exerts its tumor suppressive effects is not fully understood. In this study, we show that ABI3 is a phosphoprotein. Using proteomic array analysis, we showed that ABI3 modulated distinct cancer-related pathways in thyroid cancer cells. The KEA analysis found that PI3K substrates were enriched and forced expression of ABI3 markedly decreased the phosphorylation of AKT and the downstream-targeted protein pGSK3 beta. We next used immunoprecipitation combined with mass spectrometry to identify ABI3-interacting proteins that may be involved in modulating/integrating signaling pathways. We identified 37 ABI3 partners, including several components of the canonical WAVE regulatory complex (WRC) such as WAVE2/CYF1P1/NAP1, suggesting that ABI3 function might be regulated through WRC. Both, pharmacological inhibition of the PI3K/AKT pathway and mutation at residue S342 of ABI3, which is predicted to be phosphorylated by AKT, provided evidences that the non-phosphorylated form of ABI3 is preferentially present in the WRC protein complex. Collectively, our findings suggest that ABI3 might be a downstream mediator of the PI3K/AKT pathway that might disrupt WRC via ABI3 phosphorylation.
Keywords ABI3
follicular thyroid carcinoma
WAVE2
CYFIP1
PI3K/AKT
xmlui.dri2xhtml.METS-1.0.item-coverage Orchard Park
Language English
Sponsor Sao Paulo State Research Foundation (FAPESP)
Grant number FAPESP: 2013/03867-5
FAPESP: 2014/046570-6
Date 2017
Published in Oncotarget. Orchard Park, v. 8, n. 40, p. 67769-67781, 2017.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 67769-67781
Origin https://doi.org/10.18632/oncotarget.18840
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000410790500078
URI https://repositorio.unifesp.br/handle/11600/57356

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