Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts
Autor: | Chong Zhang, Xiang-Yu Wang, Peng Zhang, Tao-Chen He, Jia-Hao Han, Rui Zhang, Jing Lin, Jie Fan, Lu Lu, Wen-Wei Zhu, Hu-Liang Jia, Ju-Bo Zhang, Jin-Hong Chen |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Cancer Research
QH573-671 Immunology Liver Neoplasms Proteins Cell Biology Epithelial-mesenchymal transition Exosomes Lipid Metabolism Cancer metabolism Article Metastasis Cellular and Molecular Neuroscience Mice MicroRNAs Cancer-Associated Fibroblasts Acetyl Coenzyme A Cell Line Tumor Animals Humans Neoplasm Metastasis Cytology Colorectal Neoplasms |
Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 13, Iss 1, Pp 1-14 (2022) |
ISSN: | 2041-4889 |
Popis: | Abstract Tumor metastasis is a hallmark of cancer. The communication between cancer-derived exosomes and stroma plays an irreplaceable role in facilitating pre-metastatic niche formation and cancer metastasis. However, the mechanisms underlying exosome-mediated pre-metastatic niche formation during colorectal cancer (CRC) liver metastasis remain incompletely understood. Here we identified HSPC111 was the leading upregulated gene in hepatic stellate cells (HSCs) incubated with CRC cell-derived exosomes. In xenograft mouse model, CRC cell-derived exosomal HSPC111 facilitated pre-metastatic niche formation and CRC liver metastases (CRLM). Consistently, CRC patients with liver metastasis had higher level of HSPC111 in serum exosomes, primary tumors and cancer-associated fibroblasts (CAFs) in liver metastasis than those without. Mechanistically, HSPC111 altered lipid metabolism of CAFs by phosphorylating ATP-citrate lyase (ACLY), which upregulated the level of acetyl-CoA. The accumulation of acetyl-CoA further promoted CXCL5 expression and secretion by increasing H3K27 acetylation in CAFs. Moreover, CXCL5-CXCR2 axis reinforced exosomal HSPC111 excretion from CRC cells and promoted liver metastasis. These results uncovered that CRC cell-derived exosomal HSPC111 promotes pre-metastatic niche formation and CRLM via reprogramming lipid metabolism in CAFs, and implicate HSPC111 may be a potential therapeutic target for preventing CRLM. |
Databáze: | OpenAIRE |
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