{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alexander WB"],"funding":["NIEHS NIH HHS","Wilmot","National Cancer Institute","NCI NIH HHS","University of Rochester Medical Center","NIGMS NIH HHS"],"pagination":["dmm050358"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10924230"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(6)"],"pubmed_abstract":["Cholangiocarcinoma (CCA) is a deadly and heterogeneous type of cancer characterized by a spectrum of epidemiologic associations as well as genetic and epigenetic alterations. We seek to understand how these features inter-relate in the earliest phase of cancer development and through the course of disease progression. For this, we studied murine models of liver injury integrating the most commonly occurring gene mutations of CCA - including Kras, Tp53, Arid1a and Smad4 - as well as murine hepatobiliary cancer models and derived primary cell lines based on these mutations. Among commonly mutated genes in CCA, we found that Smad4 functions uniquely to restrict reactive cholangiocyte expansion to liver injury through restraint of the proliferative response. Inactivation of Smad4 accelerates c"],"journal":["Disease models & mechanisms"],"pubmed_title":["Smad4 restricts injury-provoked biliary proliferation and carcinogenesis."],"pmcid":["PMC10924230"],"funding_grant_id":["R01 CA172302","P30 ES001247","R35 GM137833","1R01CA172302"],"pubmed_authors":["Ruffolo LI","Patel A","Hill MA","Whitney-Miller CL","Georger M","Linehan DC","Friedland SC","Jackson KM","Ullman N","Alexander WB","Belt BA","Figueroa-Guilliani N","Murphy PJ","McCall MN","Wang W","Hezel AF","O'Dell MR","Guo B"],"additional_accession":[]},"is_claimable":false,"name":"Smad4 restricts injury-provoked biliary proliferation and carcinogenesis.","description":"Cholangiocarcinoma (CCA) is a deadly and heterogeneous type of cancer characterized by a spectrum of epidemiologic associations as well as genetic and epigenetic alterations. We seek to understand how these features inter-relate in the earliest phase of cancer development and through the course of disease progression. For this, we studied murine models of liver injury integrating the most commonly occurring gene mutations of CCA - including Kras, Tp53, Arid1a and Smad4 - as well as murine hepatobiliary cancer models and derived primary cell lines based on these mutations. Among commonly mutated genes in CCA, we found that Smad4 functions uniquely to restrict reactive cholangiocyte expansion to liver injury through restraint of the proliferative response. Inactivation of Smad4 accelerates c","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-07-15T12:01:37.944Z","creation":"2026-07-04T03:12:29.611Z"},"accession":"S-EPMC10924230","cross_references":{"pubmed":["38415925"],"doi":["10.1242/dmm.050358"]}}