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p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis
p16(Ink4a) and p21(Cip1/Waf1) act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16(Ink4) and p21(Cip1/Waf1), namely, tumour promotion through chemotaxis...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727112/ https://www.ncbi.nlm.nih.gov/pubmed/29234059 http://dx.doi.org/10.1038/s41467-017-02281-x |
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author | Okuma, Atsushi Hanyu, Aki Watanabe, Sugiko Hara, Eiji |
author_facet | Okuma, Atsushi Hanyu, Aki Watanabe, Sugiko Hara, Eiji |
author_sort | Okuma, Atsushi |
collection | PubMed |
description | p16(Ink4a) and p21(Cip1/Waf1) act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16(Ink4) and p21(Cip1/Waf1), namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16(Ink4) and p21(Cip1/Waf1) are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3. Thus, deletion of p16 (Ink4) and p21 (Cip1/Waf1) reduces CX3CR1 expression, thereby inhibiting Mo-MDSC accumulation in tumours expressing CX3CL1 and suppressing the tumour progression in mice. Notably, blockade of the CX3CL1/CX3CR1 axis suppresses tumour growth, whereas inactivation of CDKs elicits the opposite effect. These findings reveal an unexpected function of p16 (Ink4a) and p21 (Waf1/Cip1) and indicate that regulation of Mo-MDSCs chemotaxis is a valuable potential strategy for control of tumour development. |
format | Online Article Text |
id | pubmed-5727112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57271122017-12-14 p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis Okuma, Atsushi Hanyu, Aki Watanabe, Sugiko Hara, Eiji Nat Commun Article p16(Ink4a) and p21(Cip1/Waf1) act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16(Ink4) and p21(Cip1/Waf1), namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16(Ink4) and p21(Cip1/Waf1) are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3. Thus, deletion of p16 (Ink4) and p21 (Cip1/Waf1) reduces CX3CR1 expression, thereby inhibiting Mo-MDSC accumulation in tumours expressing CX3CL1 and suppressing the tumour progression in mice. Notably, blockade of the CX3CL1/CX3CR1 axis suppresses tumour growth, whereas inactivation of CDKs elicits the opposite effect. These findings reveal an unexpected function of p16 (Ink4a) and p21 (Waf1/Cip1) and indicate that regulation of Mo-MDSCs chemotaxis is a valuable potential strategy for control of tumour development. Nature Publishing Group UK 2017-12-12 /pmc/articles/PMC5727112/ /pubmed/29234059 http://dx.doi.org/10.1038/s41467-017-02281-x Text en © The Author(s) 2017 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/. |
spellingShingle | Article Okuma, Atsushi Hanyu, Aki Watanabe, Sugiko Hara, Eiji p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title | p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title_full | p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title_fullStr | p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title_full_unstemmed | p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title_short | p16(Ink4a) and p21(Cip1/Waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
title_sort | p16(ink4a) and p21(cip1/waf1) promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727112/ https://www.ncbi.nlm.nih.gov/pubmed/29234059 http://dx.doi.org/10.1038/s41467-017-02281-x |
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