We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role.
- Authors
Yu, Junhui; Xu, Zhengshui; Guo, Jing; Yang, Kui; Zheng, Jianbao; Sun, Xuejun
- 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.
- Subjects
MACROPHAGES; COLON cancer prognosis; COLON cancer treatment; DISEASE progression; CYCLINS; PROMOTERS (Genetics)
- Publication
Cell Death Discovery, 2021, Vol 7, Issue 1, p1
- ISSN
2058-7716
- Publication type
Article
- DOI
10.1038/s41420-021-00730-7