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Title: N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP
Authors: Chung, Yat Joong
Salvi, Amrita
Kalailingam, Pazhanichamy
Alnawaz, Myra
Tan, Suat Hoon
Pan, Jiun Yit
Tan, Nguan Soon
Thanabalu, Thirumaran
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Chung, 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-.
Project: MOE 2013-T2-2-031 
Journal: Biology 
Abstract: Neural 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.
ISSN: 2079-7737
DOI: 10.3390/biology11040582
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
School of Biological Sciences 
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/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
SBS Journal Articles

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