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Sökning: WFRF:(Levy Lahad Ephrat) > BRCA mutational sta...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005522naa a2200649 4500
001oai:DiVA.org:liu-190123
003SwePub
008221123s2022 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1901232 URI
0247 a https://doi.org/10.1038/s41467-022-34081-32 DOI
040 a (SwePub)liu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Shaashua, Leeu Weizmann Inst Sci, Israel4 aut
2451 0a BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling
264 c 2022-10-31
264 1b Nature Portfolio,c 2022
338 a electronic2 rdacarrier
500 a Funding Agencies|Thompson Family Foundation; ISF [395/21]; ERC [754320]; Laura Gurwin Flug Family Fund; Peter Award; Comisaroff Family Trust; Estate of Annice Anzelewitz; Estate of Mordecai M. Roshwal; Rising Tide Foundation; MSK [P30 CA008748]; NIH [R35GM118173, U01TR002625]; Patricia Gruber Award
520 a Tumors 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. Cancer-associated fibroblasts are transcriptionally rewired by signals from the cancer cells, resulting in heterogeneous populations. Here the authors show that loss of BRCA function in pancreatic cancer cells leads to HSF1-dependent accumulation of immune-regulatory clusterin-positive cancer associated fibroblasts.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
7001 a Ben-Shmuel, Aviadu Weizmann Inst Sci, Israel4 aut
7001 a Pevsner-Fischer, Meiravu Weizmann Inst Sci, Israel4 aut
7001 a Friedman, Gilu Weizmann Inst Sci, Israel4 aut
7001 a Levi-Galibov, Oshratu Weizmann Inst Sci, Israel4 aut
7001 a Nandakumar, Subhikshau Mem Sloan Kettering Canc Ctr, NY 10021 USA4 aut
7001 a Barki, Debrau Weizmann Inst Sci, Israel4 aut
7001 a Nevo, Reinatu Weizmann Inst Sci, Israel4 aut
7001 a Brown, Lauren E.u Boston Univ, MA 02215 USA; Boston Univ, MA 02215 USA4 aut
7001 a Zhang, Wenhanu Boston Univ, MA 02215 USA; Boston Univ, MA 02215 USA4 aut
7001 a Stein, Yanivu Weizmann Inst Sci, Israel4 aut
7001 a Lior, Chenu Weizmann Inst Sci, Israel4 aut
7001 a Kim, Han Sangu Weill Cornell Med, NY USA; Weill Cornell Med, NY USA; Yonsei Univ, South Korea4 aut
7001 a Bojmar, Lindau Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Weill Cornell Med, NY USA; Weill Cornell Med, NY USA4 aut0 (Swepub:liu)linbo68
7001 a Jarnagin, William R.u Mem Sloan Kettering Canc Ctr, NY 10021 USA4 aut
7001 a Lecomte, Nicolasu Mem Sloan Kettering Canc Ctr, NY 10021 USA4 aut
7001 a Mayer, Shimritu Weizmann Inst Sci, Israel4 aut
7001 a Stok, Roniu Weizmann Inst Sci, Israel4 aut
7001 a Bishara, Hendu Weizmann Inst Sci, Israel4 aut
7001 a Hamodi, Rawandu Weizmann Inst Sci, Israel4 aut
7001 a Levy-Lahad, Ephratu Hebrew Univ Jerusalem, Israel4 aut
7001 a Golan, Taliau Tel Aviv Univ, Israel4 aut
7001 a Porco, John A. Jr.u Boston Univ, MA 02215 USA; Boston Univ, MA 02215 USA4 aut
7001 a Iacobuzio-Donahue, Christine A.u Mem Sloan Kettering Canc Ctr, NY 10021 USA4 aut
7001 a Schultz, Nikolausu Mem Sloan Kettering Canc Ctr, NY 10021 USA4 aut
7001 a Tuveson, David A.u Cold Spring Harbor Lab, NY USA4 aut
7001 a Lyden, Davidu Weill Cornell Med, NY USA; Weill Cornell Med, NY USA4 aut
7001 a Kelsen, Davidu Weill Cornell Med Coll, NY USA4 aut
7001 a Scherz-Shouval, Ruthu Weizmann Inst Sci, Israel4 aut
7102 a Weizmann Inst Sci, Israelb Mem Sloan Kettering Canc Ctr, NY 10021 USA4 org
7730 t Nature Communicationsd : Nature Portfoliog 13:1q 13:1x 2041-1723
8564 u https://liu.diva-portal.org/smash/get/diva2:1713013/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-190123
8564 8u https://doi.org/10.1038/s41467-022-34081-3

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