Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.
Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.
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肿瘤相关巨噬细胞（TAM）依赖于MMP 1的促癌作用。
DOI：
10.1038/s41420-021-00730-7
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发表时间：
2021-11-09
影响因子：
7
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Yu J;Xu Z;Guo J;Yang K;Zheng J;Sun X
肿瘤相关巨噬细胞（TAM）和肿瘤细胞之间通过几种可溶性因子和信号传导的复杂相互作用对结直肠癌（CRC）的进展至关重要。然而，涉及的分子机制仍然难以捉摸。在这项研究中，我们证明了来自TAMs的MMP 1通过加速细胞周期从G 0/G1期到S期和G2/M期的转变而显著促进结肠癌细胞的增殖。此外，外源性MMP 1通过改变c-Myc和ETV 4激活cdc 25 a/CDK 4-cyclin D1和p21/cdc 2-cyclin B1复合物。机制研究表明，抑制PAR 1或阻断MAPK/Erk信号通路可消除外源性MMP 1诱导的体外和体内增殖。ETV 4能与MMP 1的启动子结合，激活MMP 1的转录，证实了MMP 1/ETV 4/MMP 1的正反馈。总之，我们的研究确定了结肠癌细胞和TAM之间的细胞因子旁分泌方式。MMP 1/PAR 1/Erk 1/2/ETV 4正反馈环可能是结直肠癌的治疗靶点和预后指标。
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.
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影响因子：
11.2
作者：
Juncker-Jensen A;Deryugina EI;Rimann I;Zajac E;Kupriyanova TA;Engelholm LH;Quigley JP
通讯作者：
Quigley JP
影响因子：
9.7
作者：
Liu, Min;Hu, Yi;Yang, Hong
通讯作者：
Yang, Hong
影响因子：
1.9
作者：
Langenskiold, Marcus;Ivarsson, Marie-Lois;Angenete, Eva
通讯作者：
Angenete, Eva
影响因子：
2.4
作者：
Du, Xilin;Wang, Shengzhi;Li, Jinmao
通讯作者：
Li, Jinmao
影响因子：
64.5
作者：
Boire, A;Covic, L;Kuliopulos, A
通讯作者：
Kuliopulos, A