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Cited by 22Thyroid Cancer Diagnosis and TreatmentPI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase Signaling

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

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Moraes, Lais, Zanchin, Nilson I.T., Cerutti, Janete M.·2017·Oncotarget
DOI 10.18632/oncotarget.18840PMC PMC5620210
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Abstract

// Lais Moraes 1 , Nilson I.T. Zanchin 2 and Janete M. Cerutti 1 1 Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil 2 Instituto Carlos Chagas, Fundação Oswaldo Cruz/FIOCRUZ, Curitiba, Paraná, Brazil Correspondence to: Janete M. Cerutti, email: j.cerutti@unifesp.br Keywords: ABI3 , follicular thyroid carcinoma, WAVE2, CYFIP1, PI3K/AKT Received: June 29, 2016 Accepted: June 04, 2017 Published: June 29, 2017 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 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.

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  • Non-phosphorylated form of ABI3 is preferentially incorporated in WRC, while the phosphorylated form represents an inactive protein not included in the complex.

    “Non-phosphorylated form of ABI3 is preferentially incorporated in WRC, while the phosphorylated form represents an inactive protein not included in the complex.”

    From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [26]

    The Results ('WAVE 2 and CYFIP1 are ABI3-interacting proteins') report that non-phosphorylated ABI3 preferentially co-precipitated with WAVE2. They say only that phosphorylation *may* generate an inactive form unable to interact with WAVE2; the Discussion likewise presents inhibition of WRC formation as a proposed model. The claim overstates that proposed interpretation as an established fact. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ABI3 serves as a downstream mediator of the PI3K/AKT pathway that disrupts WRC via phosphorylation of ABI3.

    “ABI3 serves as a downstream mediator of the PI3K/AKT pathway that disrupts WRC via phosphorylation of ABI3 (26).”

    From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [26]

    The Discussion proposes that PI3K/AKT signaling controls ABI3 phosphorylation and that phosphorylated ABI3 inhibits WRC formation. It presents this as a suggested model, however, rather than establishing the unqualified mechanism stated in the citing sentence. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ABI3 is phosphorylated at Ser342 by signaling through the PI3K/AKT pathway.

    “ABI3 is phosphorylated at Ser342 by signaling through the PI3K/AKT pathway.”

    From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [26]

    The Results section reports that the S342A mutation and PI3K/AKT inhibition shift ABI3 toward its non-phosphorylated form. The Discussion interprets this as suggesting that PI3K/AKT potentially phosphorylates ABI3 at S342; it does not establish the claim's unqualified pathway attribution, and the Results note that another pathway might phosphorylate S342 in one cell line. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ABI3 is believed to be involved in actin cytoskeleton regulation by participating in the WAVE regulatory complexes, but its exact function in the cell remains unknown.

    “Similar to other ABI proteins, ABI3 is also believed to be involved in the actin cytoskeleton regulation by participating in the WASP family Verprolin homolog protein (WAVE) regulatory complexes (WRC), but its exact function in the cell remains unknown 5 .”

    From ABI3 deletion in TgCRND8 mice is associated with reduced amyloid plaque pathology and altered glial response (2023) · cites this paper as [5]

    The Introduction identifies ABI3 as a WAVE regulatory complex component, and the Results report its interaction with WAVE2 and CYFIP1, supporting the proposed link to actin-cytoskeleton regulation. The Introduction says the precise mechanism of ABI3’s cytoskeleton-remodeling effect in thyroid cells is unknown; it does not establish that ABI3’s exact function is unknown in cells generally. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • ABI3 participates in the WAVE regulatory complex, which is involved in actin cytoskeleton organization.

    “It participates in the WASP-family verprolin homologous protein (WAVE) regulatory complex, which is involved in actin cytoskeleton organization (20, 21).”

    From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [21]

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Research works printed but not linked: 38

  1. [1]Latini FR Hemerly JP Freitas BC Oler G Riggins GJ Cerutti JM ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence BMC Cancer 2011 11 11 21223585 PMC3032749
  2. [2]Moraes L Galrao AL Rubio I Cerutti JM Transcriptional regulation of the potential tumor suppressor ABI3 gene in thyroid carcinomas: interplay between methylation and NKX2-1 availability Oncotarget 2016 7 25960 25970 10.18632/oncotarget.8416 27036019 PMC5041957 · DOI
  3. [3]Ichigotani Y Yokozaki S Fukuda Y Hamaguchi M Matsuda S Forced expression of NESH suppresses motility and metastatic dissemination of malignant cells Cancer Res 2002 62 2215 2219 11956071
  4. [4]Hirao N Sato S Gotoh T Maruoka M Suzuki J Matsuda S Shishido T Tani K NESH (Abi-3) is present in the Abi/WAVE complex but does not promote c-Abl-mediated phosphorylation FEBS Lett 2006 580 6464 6470 17101133
  5. [5]Bae J Sung BH Cho IH Kim SM Song WK NESH regulates dendritic spine morphology and synapse formation PLoS One 2012 7 e34677 22485184 PMC3317636
  6. [6]Bae J Sung BH Cho IH Song WK F-actin-dependent regulation of NESH dynamics in rat hippocampal neurons PLoS One 2012 7 e34514 22496823 PMC3319579
  7. [7]Kanduri M Cahill N Goransson H Enstrom C Ryan F Isaksson A Rosenquist R Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia Blood 2010 115 296 305 19897574
  8. [8]Dai Z Pendergast AM Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity Genes Dev 1995 9 2569 2582 7590236
  9. [9]Chen B Brinkmann K Chen Z Pak CW Liao Y Shi S Henry L Grishin NV Bogdan S Rosen MK The WAVE regulatory complex links diverse receptors to the actin cytoskeleton Cell 2014 156 195 207 24439376 PMC4059610
  10. [10]Chen EY Tan CM Kou Y Duan Q Wang Z Meirelles GV Clark NR Ma'ayan A Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool BMC Bioinformatics 2013 14 128 23586463 PMC3637064
  11. [11]Chen XJ Squarr AJ Stephan R Chen B Higgins TE Barry DJ Martin MC Rosen MK Bogdan S Way M Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton Dev Cell 2014 30 569 584 25203209 PMC4165403
  12. [12]Eden S Rohatgi R Podtelejnikov AV Mann M Kirschner MW Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck Nature 2002 418 790 793 12181570
  13. [13]Takenawa T Suetsugu S The WASP-WAVE protein network: connecting the membrane to the cytoskeleton Nat Rev Mol Cell Biol 2007 8 37 48 17183359
  14. [14]Gautreau A Ho HY Li J Steen H Gygi SP Kirschner MW Purification and architecture of the ubiquitous Wave complex Proc Natl Acad Sci U S A 2004 101 4379 4383 15070726 PMC384755
  15. [15]Leng Y Zhang J Badour K Arpaia E Freeman S Cheung P Siu M Siminovitch K Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation Proc Natl Acad Sci U S A 2005 102 1098 1103 15657136 PMC545868
  16. [16]Chen Z Borek D Padrick SB Gomez TS Metlagel Z Ismail AM Umetani J Billadeau DD Otwinowski Z Rosen MK Structure and control of the actin regulatory WAVE complex Nature 2010 468 533 538 21107423 PMC3085272
  17. [17]Han G Ye M Liu H Song C Sun D Wu Y Jiang X Chen R Wang C Wang L Zou H Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis Electrophoresis 2010 31 1080 1089 20166139
  18. [18]Sekino S Kashiwagi Y Kanazawa H Takada K Baba T Sato S Inoue H Kojima M Tani K The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex Cell Commun Signal 2015 13 41 26428302 PMC4589964
  19. [19]Huttlin EL Jedrychowski MP Elias JE Goswami T Rad R Beausoleil SA Villen J Haas W Sowa ME Gygi SP A tissue-specific atlas of mouse protein phosphorylation and expression Cell 2010 143 1174 1189 21183079 PMC3035969
  20. [20]Manes NP Dong L Zhou W Du X Reghu N Kool AC Choi D Bailey CL Petricoin EF 3rd Liotta LA Popov SG Discovery of mouse spleen signaling responses to anthrax using label-free quantitative phosphoproteomics via mass spectrometry Mol Cell Proteomics 2011 10 M110 000927 PMC3047145 21189417
  21. [21]Raijmakers R Kraiczek K de Jong AP Mohammed S Heck AJ Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase-TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to a quadrupole time-of-flight mass spectrometer Anal Chem 2010 82 824 832 20058876
  22. [22]Latini FR Hemerly JP Oler G Riggins GJ Cerutti JM Re-expression of ABI3-binding protein suppresses thyroid tumor growth by promoting senescence and inhibiting invasion Endocr Relat Cancer 2008 15 787 799 18559958 PMC2742300
  23. [23]Andrade BM Carvalho DP Perspectives of adenosine monophosphate activated kinase (AMPK) signalling pathway in thyroid cancer Bioscience reports 2014 PMC3986867 27919039
  24. [24]Davis RJ Signal transduction by the JNK group of MAP kinases Cell 2000 103 239 252 11057897
  25. [25]Xing M Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer Thyroid 2010 20 697 706 20578891 PMC2935335
  26. [26]Abbosh PH Nephew KP Multiple signaling pathways converge on beta-catenin in thyroid cancer Thyroid 2005 15 551 561 16029121
  27. [27]Garcia-Rostan G Camp RL Herrero A Carcangiu ML Rimm DL Tallini G Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis Am J Pathol 2001 158 987 996 11238046 PMC1850336
  28. [28]Cancer Genome Atlas Research N Integrated genomic characterization of papillary thyroid carcinoma Cell 2014 159 676 690 25417114 PMC4243044
  29. [29]Stuart JR Gonzalez FH Kawai H Yuan ZM c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading J Biol Chem 2006 281 31290 31297 16899465
  30. [30]Yamaguchi H Condeelis J Regulation of the actin cytoskeleton in cancer cell migration and invasion Biochim Biophys Acta 2007 1773 642 652 16926057 PMC4266238
  31. [31]Jia S Jia Y Weeks HP Ruge F Feng X Ma R Ji J Ren J Jiang WG Down-regulation of WAVE2, WASP family verprolin-homologous protein 2, in gastric cancer indicates lymph node metastasis and cell migration Anticancer Res 34 2185 2194 24778020
  32. [32]Kurisu S Suetsugu S Yamazaki D Yamaguchi H Takenawa T Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells Oncogene 2005 24 1309 1319 15608687
  33. [33]Semba S Iwaya K Matsubayashi J Serizawa H Kataba H Hirano T Kato H Matsuoka T Mukai K Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung Clin Cancer Res 2006 12 2449 2454 16638851
  34. [34]Silva JM Ezhkova E Silva J Heart S Castillo M Campos Y Castro V Bonilla F Cordon-Cardo C Muthuswamy SK Powers S Fuchs E Hannon GJ Cyfip1 is a putative invasion suppressor in epithelial cancers Cell 2009 137 1047 1061 19524508 PMC2754270
  35. [35]Escobar B de Carcer G Fernandez-Miranda G Cascon A Bravo-Cordero JJ Montoya MC Robledo M Canamero M Malumbres M Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation Cancer Res 70 9349 9359 20861187
  36. [36]Schober M Raghavan S Nikolova M Polak L Pasolli HA Beggs HE Reichardt LF Fuchs E Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics J Cell Biol 2007 176 667 680 17325207 PMC2064024
  37. [37]Toutant M Costa A Studler JM Kadare G Carnaud M Girault JA Alternative splicing controls the mechanisms of FAK autophosphorylation Mol Cell Biol 2002 22 7731 7743 12391143 PMC134714
  38. [38]Kotula L Abi1, a critical molecule coordinating actin cytoskeleton reorganization with PI-3 kinase and growth signaling FEBS letters 2012 586 2790 2794 22617151 PMC4521604

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Authors
Moraes, L., Zanchin, N. I. T., & Cerutti, J. M.
Affiliations
  • Universidade Federal de São Paulo (BR)
  • Instituto Carlos Chagas (BR)
Corresponding author
Cerutti, Janete M.
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-06-29
Volume
8
Issue
40
Pages
67769-67781
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.18840
PMC
PMC5620210
OpenAlex
W2733874486
Cited by
22
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 1 · 2017: 1
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
Funders
  • Fundação de Amparo à Pesquisa do Estado de São Paulo (13/03867-5, 2014/)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (2013/03867-5)
  • Fundação Oswaldo Cruz
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
ABI3, WAVE2, WAVE regulatory complex, CYFIP1, PI3K/Akt signaling, follicular thyroid carcinoma, tumor suppressor, protein phosphorylation, Akt, GSK3β, protein-protein interaction

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