guest ::
| Home > Publications database > Malformin C preferentially kills glioblastoma stem-like cells via concerted induction of proteotoxic stress and autophagic flux blockade. > print |
| Home > Publications database > Malformin C preferentially kills glioblastoma stem-like cells via concerted induction of proteotoxic stress and autophagic flux blockade. > print |
| 001 | 294336 | ||
| 005 | 20250310103210.0 | ||
| 024 | 7 | _ | |a 10.1002/1878-0261.13756 |2 doi |
| 024 | 7 | _ | |a pmid:39462997 |2 pmid |
| 024 | 7 | _ | |a 1574-7891 |2 ISSN |
| 024 | 7 | _ | |a 1878-0261 |2 ISSN |
| 024 | 7 | _ | |a altmetric:169807705 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2024-02169 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Phillips, Emma |0 P:(DE-He78)830be4979a39935ac6272eaebad5982a |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Malformin C preferentially kills glioblastoma stem-like cells via concerted induction of proteotoxic stress and autophagic flux blockade. |
| 260 | _ | _ | |a Hoboken, NJ |c 2025 |b John Wiley & Sons, Inc. |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1741599076_15764 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:B067#LA:B067# / 2025 Mar;19(3):785-807 |
| 520 | _ | _ | |a Glioblastoma is a highly aggressive brain tumor for which there is no cure. The dire prognosis of this disease is largely attributable to a high level of heterogeneity, including the presence of a subpopulation of tumor-initiating glioblastoma stem-like cells (GSCs), which are refractory to chemo- and radiotherapy. Here, in an unbiased marine-derived fungal extract screen, together with bioguided dereplication based on high-resolution mass spectrometry, we identified malformin C to preferentially induce cell death in patient-derived GSCs and explore the potential of this cyclic peptide as a therapeutic agent for glioblastoma. Malformin C significantly reduced tumor growth in an in vivo xenograft model of glioblastoma. Using transcriptomics and chemoproteomics, we found that malformin C binds to many proteins, leading to their aggregation, and rapidly induces the unfolded protein response, including autophagy, in GSCs. Crucially, chemical inhibition of translation using cycloheximide rescued malformin C-induced cell death in GSCs, demonstrating that the proteotoxic effect of the compound is necessary for its cytotoxicity. At the same time, malformin C appears to accumulate in lysosomes, disrupting autophagic flux, and driving cells to death. Supporting this, malformin C synergizes with chloroquine, an inhibitor of autophagy. Strikingly, we observed that autophagic flux is differentially regulated in GSCs compared with normal astrocytes. The sensitivity of GSCs to malformin C highlights the relevance of proteostasis and autophagy as a therapeutic vulnerability in glioblastoma. |
| 536 | _ | _ | |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312) |0 G:(DE-HGF)POF4-312 |c POF4-312 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a autophagy |2 Other |
| 650 | _ | 7 | |a cancer |2 Other |
| 650 | _ | 7 | |a compound screen |2 Other |
| 650 | _ | 7 | |a glioblastoma |2 Other |
| 650 | _ | 7 | |a proteostasis |2 Other |
| 650 | _ | 7 | |a stem cells |2 Other |
| 650 | _ | 7 | |a unfolded protein response |2 Other |
| 700 | 1 | _ | |a van Enk, Sizèd |0 P:(DE-He78)182bfcd26a8ff245bf9d349bed715e33 |b 1 |u dkfz |
| 700 | 1 | _ | |a Kildgaard, Sara |b 2 |
| 700 | 1 | _ | |a Schlue, Silja |0 P:(DE-He78)880900065fdfb634b00cd591b801ee42 |b 3 |u dkfz |
| 700 | 1 | _ | |a Göttmann, Mona |0 P:(DE-He78)442ee8f54d846d943023a916889feb8e |b 4 |
| 700 | 1 | _ | |a Jennings, Lauren Victoria |0 P:(DE-He78)f9436ab13c30938772ee246bd6920734 |b 5 |
| 700 | 1 | _ | |a Bethke, Frederic |0 P:(DE-He78)06d81b4a485d027b97543964b7035573 |b 6 |u dkfz |
| 700 | 1 | _ | |a Müller, Gabriele |0 P:(DE-He78)e490480a4e3d9a6a3a4f1408ca599590 |b 7 |u dkfz |
| 700 | 1 | _ | |a Herold-Mende, Christel |b 8 |
| 700 | 1 | _ | |a Pastor-Flores, Daniel |0 P:(DE-HGF)0 |b 9 |
| 700 | 1 | _ | |a Schneider, Martin |0 P:(DE-He78)0d37cc734b95fed555f2244d6fee6320 |b 10 |u dkfz |
| 700 | 1 | _ | |a Helm, Dominic |0 P:(DE-He78)daaed5a5b968028e6e95d273150d5ab1 |b 11 |u dkfz |
| 700 | 1 | _ | |a Ostenfeld Larsen, Thomas |b 12 |
| 700 | 1 | _ | |a Goidts, Violaine |0 0000-0001-9046-4893 |b 13 |e Last author |
| 773 | _ | _ | |a 10.1002/1878-0261.13756 |g p. 1878-0261.13756 |0 PERI:(DE-600)2322586-5 |n 3 |p 785-807 |t Molecular oncology |v 19 |y 2025 |x 1574-7891 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:294336 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 0 |6 P:(DE-He78)830be4979a39935ac6272eaebad5982a |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 1 |6 P:(DE-He78)182bfcd26a8ff245bf9d349bed715e33 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 3 |6 P:(DE-He78)880900065fdfb634b00cd591b801ee42 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 4 |6 P:(DE-He78)442ee8f54d846d943023a916889feb8e |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 5 |6 P:(DE-He78)f9436ab13c30938772ee246bd6920734 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 6 |6 P:(DE-He78)06d81b4a485d027b97543964b7035573 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 7 |6 P:(DE-He78)e490480a4e3d9a6a3a4f1408ca599590 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 9 |6 P:(DE-HGF)0 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 10 |6 P:(DE-He78)0d37cc734b95fed555f2244d6fee6320 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 11 |6 P:(DE-He78)daaed5a5b968028e6e95d273150d5ab1 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 13 |6 0000-0001-9046-4893 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-312 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Funktionelle und strukturelle Genomforschung |x 0 |
| 914 | 1 | _ | |y 2024 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b MOL ONCOL : 2022 |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0501 |2 StatID |b DOAJ Seal |d 2023-01-06T16:01:33Z |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0500 |2 StatID |b DOAJ |d 2023-01-06T16:01:33Z |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b DOAJ : Open peer review |d 2023-01-06T16:01:33Z |
| 915 | _ | _ | |a Creative Commons Attribution CC BY (No Version) |0 LIC:(DE-HGF)CCBYNV |2 V:(DE-HGF) |b DOAJ |d 2023-01-06T16:01:33Z |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2023-10-25 |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2023-10-25 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2023-10-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2023-10-25 |
| 915 | _ | _ | |a IF >= 5 |0 StatID:(DE-HGF)9905 |2 StatID |b MOL ONCOL : 2022 |d 2023-10-25 |
| 915 | _ | _ | |a Article Processing Charges |0 StatID:(DE-HGF)0561 |2 StatID |d 2023-10-25 |
| 915 | _ | _ | |a Fees |0 StatID:(DE-HGF)0700 |2 StatID |d 2023-10-25 |
| 920 | 2 | _ | |0 I:(DE-He78)B067-20160331 |k B067 |l B067 Juniorgruppe Brain Tumor Translational Target |x 0 |
| 920 | 1 | _ | |0 I:(DE-He78)B067-20160331 |k B067 |l B067 Juniorgruppe Brain Tumor Translational Target |x 0 |
| 920 | 1 | _ | |0 I:(DE-He78)A160-20160331 |k A160 |l A160 Redoxregulation |x 1 |
| 920 | 1 | _ | |0 I:(DE-He78)W120-20160331 |k W120 |l Proteomics |x 2 |
| 920 | 0 | _ | |0 I:(DE-He78)B067-20160331 |k B067 |l B067 Juniorgruppe Brain Tumor Translational Target |x 0 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)B067-20160331 |
| 980 | _ | _ | |a I:(DE-He78)A160-20160331 |
| 980 | _ | _ | |a I:(DE-He78)W120-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|