Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role

Abstract The complex interaction between tumor-associated macrophages (TAMs) and tumor cells through several soluble factors and signaling is essential for colorectal cancer (CRC) progression. However, the molecular mechanism involved remains elusive. In this study, we demonstrated that MMP1 derived...

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Autores principales:	Junhui Yu, Zhengshui Xu, Jing Guo, Kui Yang, Jianbao Zheng, Xuejun Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/2668e56bcd8241789598744398ac7238
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spelling	oai:doaj.org-article:2668e56bcd8241789598744398ac72382021-11-14T12:12:35ZTumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role10.1038/s41420-021-00730-72058-7716https://doaj.org/article/2668e56bcd8241789598744398ac72382021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00730-7https://doaj.org/toc/2058-7716Abstract The complex interaction between tumor-associated macrophages (TAMs) and tumor cells through several soluble factors and signaling is essential for colorectal cancer (CRC) progression. However, the molecular mechanism involved remains elusive. In this study, we demonstrated that MMP1 derived from TAMs markedly facilitated colon cancer cell proliferation via accelerating cell cycle transition from G0/G1 to S and G2/M phase. Moreover, exogenous MMP1 activated cdc25a/CDK4-cyclin D1 and p21/cdc2-cyclin B1 complexes through altering c-Myc and ETV4. Mechanistic studies indicated that inhibition of PAR1 or blockage of MAPK/Erk signaling eliminated the proliferation induced by exogenous MMP1 in vitro and in vivo. In addition, ETV4 could bind to the promoter of MMP1 and activate MMP1 transcription, which confirmed the MMP1/ETV4/MMP1 positive feedback. Altogether, our study identified a cytokine paracrine manner between colon cancer cells and TAMs. MMP1/PAR1/Erk1/2/ETV4 positive feedback loop may represent to be a therapeutic target and prognostic marker in CRC.Junhui YuZhengshui XuJing GuoKui YangJianbao ZhengXuejun SunNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Junhui Yu Zhengshui Xu Jing Guo Kui Yang Jianbao Zheng Xuejun Sun Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
description	Abstract The complex interaction between tumor-associated macrophages (TAMs) and tumor cells through several soluble factors and signaling is essential for colorectal cancer (CRC) progression. However, the molecular mechanism involved remains elusive. In this study, we demonstrated that MMP1 derived from TAMs markedly facilitated colon cancer cell proliferation via accelerating cell cycle transition from G0/G1 to S and G2/M phase. Moreover, exogenous MMP1 activated cdc25a/CDK4-cyclin D1 and p21/cdc2-cyclin B1 complexes through altering c-Myc and ETV4. Mechanistic studies indicated that inhibition of PAR1 or blockage of MAPK/Erk signaling eliminated the proliferation induced by exogenous MMP1 in vitro and in vivo. In addition, ETV4 could bind to the promoter of MMP1 and activate MMP1 transcription, which confirmed the MMP1/ETV4/MMP1 positive feedback. Altogether, our study identified a cytokine paracrine manner between colon cancer cells and TAMs. MMP1/PAR1/Erk1/2/ETV4 positive feedback loop may represent to be a therapeutic target and prognostic marker in CRC.
format	article
author	Junhui Yu Zhengshui Xu Jing Guo Kui Yang Jianbao Zheng Xuejun Sun
author_facet	Junhui Yu Zhengshui Xu Jing Guo Kui Yang Jianbao Zheng Xuejun Sun
author_sort	Junhui Yu
title	Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
title_short	Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
title_full	Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
title_fullStr	Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
title_full_unstemmed	Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
title_sort	tumor-associated macrophages (tams) depend on mmp1 for their cancer-promoting role
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/2668e56bcd8241789598744398ac7238
work_keys_str_mv	AT junhuiyu tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole AT zhengshuixu tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole AT jingguo tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole AT kuiyang tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole AT jianbaozheng tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole AT xuejunsun tumorassociatedmacrophagestamsdependonmmp1fortheircancerpromotingrole
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Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role

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