Dataset Information

CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

ABSTRACT: 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-β to inhibit this process. After secretion, CCL7/CCR1 activated downstream CBP/P300 to acetylate KLF5 to promote CXCL5 transcription, while TGF-β 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-β. 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.

SUBMITTER: Xu Z

PROVIDER: S-EPMC9171262 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

Xu Zhuoqing Z Gao Han H Zhang Yuchen Y Feng Wenqing W Miao Yiming Y Xu Zifeng Z Li Wenchang W Chen Fangqian F Lv Zeping Z Huo Jianting J Liu Wangyi W Shen Xiaohui X Zong Yaping Y Zhao Jingkun J Lu Aiguo A

Molecular therapy : the journal of the American Society of Gene Therapy 20220310 6

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 sec ...[more]

PMID: 35283273

Similar Datasets

Project description:Background: The deposition of calcium oxalate (CaOx) and calcium phosphate (CaP) is the most common cause of kidney stone disease (KSD). Whether KSDs caused by CaOx and CaP have common genetic targets or signaling pathways remained unclear. Methods: The present study utilized public data GSE73680 to analyze differentially expressed genes between CaOx or CaP tissues and normal tissues, respectively. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of co-DEGs were performed. The protein-protein interaction (PPI) network was constructed to identify hub genes, and the top hub gene was selected for gene set enrichment analysis (GSEA). Finally, real-time PCR of patients' urine was performed to validate the bioinformatic results. Results: In total, 155 significantly co-upregulated DEGs and 64 co-downregulated DEGs were obtained from the datasets. The Gene Ontology analysis showed that DEGs were significantly enriched in chemical stimulus in sensory perception, detection of chemical stimulus in sensory perception of smell, and olfactory receptor activity. The KEGG analysis showed that the olfactory transduction pathway was significantly enriched. According to protein-protein interaction, 10 genes were identified as the hub genes, and CCL7 was the top hub gene. The olfactory transduction, maturity-onset diabetes of the young, linoleic acid metabolism, and fat digestion and absorption were significantly enriched in the high-CCL7 subgroup by GSEA. In total, 9 patients who had primarily CaOx mixed with some CaP stones and 9 healthy subjects were enrolled. The RT-PCR results showed that CCL7 level in the stone group was significantly higher than that in the control group (p < 0.05). For the olfactory transduction pathway, the expression of OR10A5, OR9A2, and OR1L3 was significantly upregulated in the stone group compared with the control group (p < 0.05). Conclusion: CCL7 may play a key role in the development of both CaOx and CaP, and this process may depend on olfactory transduction pathway activation.

Dataset Information

CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

Publications

CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets