N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP
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. Th...
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sg-ntu-dr.10356-1607172023-02-28T17:12:48Z N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP Chung, Yat Joong Salvi, Amrita Kalailingam, Pazhanichamy Alnawaz, Myra Tan, Suat Hoon Pan, Jiun Yit Tan, Nguan Soon Thanabalu, Thirumaran Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Science::Biological sciences Cell Adhesion Actin Cytoskeleton 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. Ministry of Education (MOE) Published version This 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. 2022-08-01T07:34:40Z 2022-08-01T07:34:40Z 2022 Journal Article 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-. https://dx.doi.org/10.3390/biology11040582 2079-7737 https://hdl.handle.net/10356/160717 10.3390/biology11040582 35453780 2-s2.0-85129131622 4 11 582 en MOE 2013-T2-2-031 RG31/20 RG154/17 Biology © 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:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
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Science::Biological sciences Cell Adhesion Actin Cytoskeleton Chung, Yat Joong Salvi, Amrita Kalailingam, Pazhanichamy Alnawaz, Myra Tan, Suat Hoon Pan, Jiun Yit Tan, Nguan Soon Thanabalu, Thirumaran N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
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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. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Chung, Yat Joong Salvi, Amrita Kalailingam, Pazhanichamy Alnawaz, Myra Tan, Suat Hoon Pan, Jiun Yit Tan, Nguan Soon Thanabalu, Thirumaran |
format |
Article |
author |
Chung, Yat Joong Salvi, Amrita Kalailingam, Pazhanichamy Alnawaz, Myra Tan, Suat Hoon Pan, Jiun Yit Tan, Nguan Soon Thanabalu, Thirumaran |
author_sort |
Chung, Yat Joong |
title |
N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
title_short |
N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
title_full |
N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
title_fullStr |
N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
title_full_unstemmed |
N-WASP attenuates cell proliferation and migration through ERK2-dependent enhanced expression of TXNIP |
title_sort |
n-wasp attenuates cell proliferation and migration through erk2-dependent enhanced expression of txnip |
publishDate |
2022 |
url |
https://hdl.handle.net/10356/160717 |
_version_ |
1759855269192400896 |