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BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling

DC Field Value Language
dc.contributor.author김한상-
dc.date.accessioned2023-03-03T02:54:12Z-
dc.date.available2023-03-03T02:54:12Z-
dc.date.issued2022-10-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/192923-
dc.description.abstractTumors initiate by mutations in cancer cells, and progress through interactions of the cancer cells with non-malignant cells of the tumor microenvironment. Major players in the tumor microenvironment are cancer-associated fibroblasts (CAFs), which support tumor malignancy, and comprise up to 90% of the tumor mass in pancreatic cancer. CAFs are transcriptionally rewired by cancer cells. Whether this rewiring is differentially affected by different mutations in cancer cells is largely unknown. Here we address this question by dissecting the stromal landscape of BRCA-mutated and BRCA Wild-type pancreatic ductal adenocarcinoma. We comprehensively analyze pancreatic cancer samples from 42 patients, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA Wild-type tumors. In particular, we detect an increase in a subset of immune-regulatory clusterin-positive CAFs in BRCA-mutated tumors. Using cancer organoids and mouse models we show that this process is mediated through activation of heat-shock factor 1, the transcriptional regulator of clusterin. Our findings unravel a dimension of stromal heterogeneity influenced by germline mutations in cancer cells, with direct implications for clinical research.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE COMMUNICATIONS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCancer-Associated Fibroblasts* / metabolism-
dc.subject.MESHCarcinoma, Pancreatic Ductal* / pathology-
dc.subject.MESHClusterin* / genetics-
dc.subject.MESHClusterin* / metabolism-
dc.subject.MESHHeat Shock Transcription Factors* / genetics-
dc.subject.MESHHeat Shock Transcription Factors* / metabolism-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHPancreatic Neoplasms* / pathology-
dc.subject.MESHTumor Microenvironment / genetics-
dc.titleBRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorLee Shaashua-
dc.contributor.googleauthorAviad Ben-Shmuel-
dc.contributor.googleauthorMeirav Pevsner-Fischer-
dc.contributor.googleauthorGil Friedman-
dc.contributor.googleauthorOshrat Levi-Galibov-
dc.contributor.googleauthorSubhiksha Nandakumar-
dc.contributor.googleauthorDebra Barki-
dc.contributor.googleauthorReinat Nevo-
dc.contributor.googleauthorLauren E Brown-
dc.contributor.googleauthorWenhan Zhang-
dc.contributor.googleauthorYaniv Stein-
dc.contributor.googleauthorChen Lior-
dc.contributor.googleauthorHan Sang Kim-
dc.contributor.googleauthorLinda Bojmar-
dc.contributor.googleauthorWilliam R Jarnagin-
dc.contributor.googleauthorNicolas Lecomte-
dc.contributor.googleauthorShimrit Mayer-
dc.contributor.googleauthorRoni Stok-
dc.contributor.googleauthorHend Bishara-
dc.contributor.googleauthorRawand Hamodi-
dc.contributor.googleauthorEphrat Levy-Lahad-
dc.contributor.googleauthorTalia Golan-
dc.contributor.googleauthorJohn A Porco Jr-
dc.contributor.googleauthorChristine A Iacobuzio-Donahue-
dc.contributor.googleauthorNikolaus Schultz-
dc.contributor.googleauthorDavid A Tuveson-
dc.contributor.googleauthorDavid Lyden-
dc.contributor.googleauthorDavid Kelsen-
dc.contributor.googleauthorRuth Scherz-Shouval-
dc.identifier.doi10.1038/s41467-022-34081-3-
dc.contributor.localIdA01098-
dc.relation.journalcodeJ02293-
dc.identifier.eissn2041-1723-
dc.identifier.pmid36316305-
dc.contributor.alternativeNameKim, Han Sang-
dc.contributor.affiliatedAuthor김한상-
dc.citation.volume13-
dc.citation.number1-
dc.citation.startPage6513-
dc.identifier.bibliographicCitationNATURE COMMUNICATIONS, Vol.13(1) : 6513, 2022-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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