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Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma

For head and neck squamous cell carcinoma (HNSCC), the local invasion and distant metastasis represent the predominant causes of mortality. Targeted inhibition of chemokines and their receptors is an ongoing antitumor strategy established on the crucial roles of chemokines in cancer invasion and met...

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Autores principales: Ling, Zihang, Li, Wei, Hu, Jiaqi, Li, Yuanyuan, Deng, Miao, Zhang, Siyuan, Ren, Xianyue, Wu, Tong, Xia, Juan, Cheng, Bin, Tao, Xiaoan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854715/
https://www.ncbi.nlm.nih.gov/pubmed/35177591
http://dx.doi.org/10.1038/s41419-022-04610-5
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author Ling, Zihang
Li, Wei
Hu, Jiaqi
Li, Yuanyuan
Deng, Miao
Zhang, Siyuan
Ren, Xianyue
Wu, Tong
Xia, Juan
Cheng, Bin
Tao, Xiaoan
author_facet Ling, Zihang
Li, Wei
Hu, Jiaqi
Li, Yuanyuan
Deng, Miao
Zhang, Siyuan
Ren, Xianyue
Wu, Tong
Xia, Juan
Cheng, Bin
Tao, Xiaoan
author_sort Ling, Zihang
collection PubMed
description For head and neck squamous cell carcinoma (HNSCC), the local invasion and distant metastasis represent the predominant causes of mortality. Targeted inhibition of chemokines and their receptors is an ongoing antitumor strategy established on the crucial roles of chemokines in cancer invasion and metastasis. Herein, we showed that C-C motif chemokine ligand 2 (CCL2)- C-C motif chemokine receptor 4 (CCR4) signaling, but not the CCL2- C-C motif chemokine receptor 2 (CCR2) axis, induces the formation of the vav guanine nucleotide exchange factor 2 (Vav2)- Rac family small GTPase 1 (Rac1) complex to activate the phosphorylation of myosin light chain (MLC), which is involved in the regulation of cell motility and cancer metastasis. We identified that targeting CCR4 could effectively interrupt the activation of HNSCC invasion and metastasis induced by CCL2 without the promoting cancer relapse observed during the subsequent withdrawal period. All current findings suggested that CCL2-CCR4-Vav2-Rac1-p-MLC signaling plays an essential role in cell migration and cancer metastasis of HNSCC, and CCR4 may serve as a new potential molecular target for HNSCC therapy.
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spelling pubmed-88547152022-03-03 Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma Ling, Zihang Li, Wei Hu, Jiaqi Li, Yuanyuan Deng, Miao Zhang, Siyuan Ren, Xianyue Wu, Tong Xia, Juan Cheng, Bin Tao, Xiaoan Cell Death Dis Article For head and neck squamous cell carcinoma (HNSCC), the local invasion and distant metastasis represent the predominant causes of mortality. Targeted inhibition of chemokines and their receptors is an ongoing antitumor strategy established on the crucial roles of chemokines in cancer invasion and metastasis. Herein, we showed that C-C motif chemokine ligand 2 (CCL2)- C-C motif chemokine receptor 4 (CCR4) signaling, but not the CCL2- C-C motif chemokine receptor 2 (CCR2) axis, induces the formation of the vav guanine nucleotide exchange factor 2 (Vav2)- Rac family small GTPase 1 (Rac1) complex to activate the phosphorylation of myosin light chain (MLC), which is involved in the regulation of cell motility and cancer metastasis. We identified that targeting CCR4 could effectively interrupt the activation of HNSCC invasion and metastasis induced by CCL2 without the promoting cancer relapse observed during the subsequent withdrawal period. All current findings suggested that CCL2-CCR4-Vav2-Rac1-p-MLC signaling plays an essential role in cell migration and cancer metastasis of HNSCC, and CCR4 may serve as a new potential molecular target for HNSCC therapy. Nature Publishing Group UK 2022-02-17 /pmc/articles/PMC8854715/ /pubmed/35177591 http://dx.doi.org/10.1038/s41419-022-04610-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ling, Zihang
Li, Wei
Hu, Jiaqi
Li, Yuanyuan
Deng, Miao
Zhang, Siyuan
Ren, Xianyue
Wu, Tong
Xia, Juan
Cheng, Bin
Tao, Xiaoan
Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title_full Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title_fullStr Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title_full_unstemmed Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title_short Targeting CCL2-CCR4 axis suppress cell migration of head and neck squamous cell carcinoma
title_sort targeting ccl2-ccr4 axis suppress cell migration of head and neck squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854715/
https://www.ncbi.nlm.nih.gov/pubmed/35177591
http://dx.doi.org/10.1038/s41419-022-04610-5
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