期刊
MOLECULAR THERAPY
卷 30, 期 6, 页码 2327-2341出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2022.03.005
关键词
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资金
- National Natural Science Foundation of China [81871933, 81802326]
- Foundation of Shanghai Municipal Health Committee [202040144]
This study found that tumor-associated mesenchymal stromal cells (MSCs) promote the expression of CXCL5 in colorectal cancer (CRC) through secreting CCL7 and TGF-beta, thereby promoting the proliferation and metastasis of CRC. KLF5 plays a key role in this process and has a dual role in regulating CXCL5.
CXCL5 is overexpressed in colorectal cancer (CRC) and promotes distant metastasis and angiogenesis of tumors; however, the underlying mechanism that mediates CXCL5 overexpression in CRC remains unclear. Here, we successfully extracted and identified primary mesenchymal stromal cells (MSCs) and verified the promoting effects of tumor-associated MSCs on CRC proliferation and metastasis in vivo and in vitro. We found that MSCs not only promoted the expression of CXCL5 by secreting CCL7 but also secreted TGF-beta to inhibit this process. After secretion, CCL7/CCR1 activated downstream CBP/P300 to acetylate KLF5 to promote CXCL5 transcription, while TGF-beta reversed the effect of KLF5 on transcription activation by regulating SMAD4. Taken together, our results indicate that MSCs in the tumor microenvironment promoted the progression and metastasis of CRC and regulated the expression of CXCL5 in CRC cells by secreting CCL7 and TGF-beta. KLF5 is the key site of these processes and plays a dual role in CXCL5 regulation. MSCs and their secreted factors may serve as potential therapeutic targets in the tumor environment.
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