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Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells
BACKGROUND: Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis form...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320060/ https://www.ncbi.nlm.nih.gov/pubmed/34321041 http://dx.doi.org/10.1186/s12964-021-00763-6 |
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author | Li, Xiaopeng Ma, Guilin Guo, Wenjie Mu, Ning Wang, Yingying Liu, Xiangguo Su, Ling |
author_facet | Li, Xiaopeng Ma, Guilin Guo, Wenjie Mu, Ning Wang, Yingying Liu, Xiangguo Su, Ling |
author_sort | Li, Xiaopeng |
collection | PubMed |
description | BACKGROUND: Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive. METHODS: Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal. RESULTS: Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form. CONCLUSION: Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-021-00763-6. |
format | Online Article Text |
id | pubmed-8320060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83200602021-07-30 Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells Li, Xiaopeng Ma, Guilin Guo, Wenjie Mu, Ning Wang, Yingying Liu, Xiangguo Su, Ling Cell Commun Signal Research BACKGROUND: Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive. METHODS: Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal. RESULTS: Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form. CONCLUSION: Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-021-00763-6. BioMed Central 2021-07-28 /pmc/articles/PMC8320060/ /pubmed/34321041 http://dx.doi.org/10.1186/s12964-021-00763-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Li, Xiaopeng Ma, Guilin Guo, Wenjie Mu, Ning Wang, Yingying Liu, Xiangguo Su, Ling Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title | Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title_full | Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title_fullStr | Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title_full_unstemmed | Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title_short | Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells |
title_sort | hhex inhibits cell migration via regulating rhoa/cdc42-cfl1 axis in human lung cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320060/ https://www.ncbi.nlm.nih.gov/pubmed/34321041 http://dx.doi.org/10.1186/s12964-021-00763-6 |
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