{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zheng Z"],"funding":["Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory Cancer Transformation","the Shanghai Rising-Star Program","National Natural Science Foundation of China"],"pagination":["3810"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9736302"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(23)"],"pubmed_abstract":["The liver is the most common site for colorectal cancer (CRC)-associated metastasis. There remain unsatisfactory medications in liver metastasis given the incomplete understanding of pathogenic mechanisms. Herein, with an orthotopic implantation model fed either regular or high-fat diets (HFD), more liver metastases were associated with an expansion of conjugated bile acids (BAs), particularly taurocholic acid (TCA) in the liver, and an increased gene expression of Na<sup>+</sup>-taurocholate cotransporting polypeptide (NTCP). Such hepatic BA change was more apparently shown in the HFD group. In the same model, TCA was proven to promote liver metastases and induce a tumor-favorable microenvironment in the liver, characterizing a high level of fibroblast activation and increased proportions of myeloid-derived immune cells. Hepatic stellate cells, a liver-residing source of fibroblasts, were dose-dependently activated by TCA, and their conditioned medium significantly enhanced the migration capability of CRC cells. Blocking hepatic BA uptake with NTCP neutralized antibody can effectively repress TCA-triggered liver metastases, with an evident suppression of tumor microenvironment niche formation. This study points to a new BA-driven mechanism of CRC-associated liver metastases, suggesting that a reduction of TCA overexposure by limiting liver uptake is a potential therapeutic option for CRC-associated liver metastasis."],"journal":["Cells"],"pubmed_title":["A High Hepatic Uptake of Conjugated Bile Acids Promotes Colorectal Cancer-Associated Liver Metastasis."],"pmcid":["PMC9736302"],"funding_grant_id":["82030118","2021KJ03-12","81830120","No. 22QA1408700","82204893"],"pubmed_authors":["Zheng Z","He F","Yuan F","Zhao L","Zhang Z","Guo H","Ke Z","Jia F","Wei J","Hou X","Wang Y"],"additional_accession":[]},"is_claimable":false,"name":"A High Hepatic Uptake of Conjugated Bile Acids Promotes Colorectal Cancer-Associated Liver Metastasis.","description":"The liver is the most common site for colorectal cancer (CRC)-associated metastasis. There remain unsatisfactory medications in liver metastasis given the incomplete understanding of pathogenic mechanisms. Herein, with an orthotopic implantation model fed either regular or high-fat diets (HFD), more liver metastases were associated with an expansion of conjugated bile acids (BAs), particularly taurocholic acid (TCA) in the liver, and an increased gene expression of Na<sup>+</sup>-taurocholate cotransporting polypeptide (NTCP). Such hepatic BA change was more apparently shown in the HFD group. In the same model, TCA was proven to promote liver metastases and induce a tumor-favorable microenvironment in the liver, characterizing a high level of fibroblast activation and increased proportions of myeloid-derived immune cells. Hepatic stellate cells, a liver-residing source of fibroblasts, were dose-dependently activated by TCA, and their conditioned medium significantly enhanced the migration capability of CRC cells. Blocking hepatic BA uptake with NTCP neutralized antibody can effectively repress TCA-triggered liver metastases, with an evident suppression of tumor microenvironment niche formation. This study points to a new BA-driven mechanism of CRC-associated liver metastases, suggesting that a reduction of TCA overexposure by limiting liver uptake is a potential therapeutic option for CRC-associated liver metastasis.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2026-06-20T03:22:11.154Z","creation":"2025-04-20T03:32:07.283Z"},"accession":"S-EPMC9736302","cross_references":{"pubmed":["36497071"],"doi":["10.3390/cells11233810"]}}