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

• Published in: Oncotarget Vol. 8; no. 40; pp. 67769 - 67781
• Main Authors: Moraes, Lais, Zanchin, Nilson I T, Cerutti, Janete M
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 15.09.2017
• Subjects: Research Paper; CYFIP1; WAVE2; follicular thyroid carcinoma; ABI3; PI3K/AKT
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.18840

We previously reported that expression is lost in follicular thyroid carcinomas and its restoration significantly inhibited cell growth, invasiveness, migration, and reduced tumor growth . 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 pGSK3β. 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.