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dc.contributor.authorChung, Yat Joongen_US
dc.contributor.authorSalvi, Amritaen_US
dc.contributor.authorKalailingam, Pazhanichamyen_US
dc.contributor.authorAlnawaz, Myraen_US
dc.contributor.authorTan, Suat Hoonen_US
dc.contributor.authorPan, Jiun Yiten_US
dc.contributor.authorTan, Nguan Soonen_US
dc.contributor.authorThanabalu, Thirumaranen_US
dc.identifier.citationChung, Y. J., Salvi, A., Kalailingam, P., Alnawaz, M., Tan, S. H., Pan, J. Y., Tan, N. S. & Thanabalu, T. (2022). N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP. Biology, 11(4), 582-.
dc.description.abstractNeural Wiskott-Aldrich Syndrome Protein (N-WASP) regulates actin cytoskeleton remodeling. It has been known that reduced N-WASP expression in breast and colorectal cancers is associated with poor prognosis. Here, we found reduced N-WASP expression in squamous cell carcinoma (SCC) patient samples. The SCC cell line HSC-5 with reduced N-WASP expression was used to generate HSC-5CN (control) and HSC-5NW (N-WASP overexpression) cells. HSC-5NW cells had reduced cell proliferation and migration compared to HSC-5CN cells. HSC-5NW cells had increased phospho-ERK2 (extracellular signal-regulated kinase 2), phosphorylated Forkhead box protein class O1 (FOXO1) and reduced nuclear FOXO1 staining compared to HSC-5CN cells. Proteasome inhibition stabilized total FOXO1, however, not nuclear staining, suggesting that FOXO1 could be degraded in the cytoplasm. Inhibition of ERK2 enhanced nuclear FOXO1 levels and restored cell proliferation and migration of HSC-5NW to those of HSC-5CN cells, suggesting that ERK2 regulates FOXO1 activity. The expression of thioredoxin-interacting protein (TXNIP), a FOXO1 target that inhibits thioredoxin and glucose uptake, was higher in HSC-5NW cells than in HSC-5CN cells. Knockdown of TXNIP in HSC-5NW cells restored cell proliferation and migration to those of HSC-5CN cells. Thus, we propose that N-WASP regulates cell proliferation and migration via an N-WASP-ERK2-FOXO1-TXNIP pathway.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.relationMOE 2013-T2-2-031en_US
dc.rights© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleN-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIPen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US
dc.subject.keywordsCell Adhesionen_US
dc.subject.keywordsActin Cytoskeletonen_US
dc.description.acknowledgementThis work was supported by the Academic Research Fund Tier 2 (MOE 2013-T2-2-031) and Academic Research Fund Tier 1 (MOE) RG31/20 and RG154/17 grants from the Ministry of Education of Singapore.en_US
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