Publications by authors named "Geronimo Heilmann"

4 Publications

  • Page 1 of 1

Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis.

Cell Rep 2021 Nov;37(8):110056

Department of Medical Oncology, West German Cancer Center, University Hospital Essen at the University Duisburg-Essen, Duisburg, Germany; German Cancer Consortium (DKTK) partner site Essen, Essen, Germany. Electronic address:

Statins are among the most commonly prescribed drugs, and around every fourth person above the age of 40 is on statin medication. Therefore, it is of utmost clinical importance to understand the effect of statins on cancer cell plasticity and its consequences to not only patients with cancer but also patients who are on statins. Here, we find that statins induce a partial epithelial-to-mesenchymal transition (EMT) phenotype in cancer cells of solid tumors. Using a comprehensive STRING network analysis of transcriptome, proteome, and phosphoproteome data combined with multiple mechanistic in vitro and functional in vivo analyses, we demonstrate that statins reduce cellular plasticity by enforcing a mesenchymal-like cell state that increases metastatic seeding ability on one side but reduces the formation of (secondary) tumors on the other due to heterogeneous treatment responses. Taken together, we provide a thorough mechanistic overview of the consequences of statin use for each step of cancer development, progression, and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.110056DOI Listing
November 2021

Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family.

Chemistry 2020 Jul 17;26(39):8524-8531. Epub 2020 Jun 17.

Chemische Biologie, Universität Duisburg-Essen, ZMB, Fakultät für Biologie, Universitätsstr. 2, 45117, Essen, Germany.

Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural similarities as well as differences to the argyrin NP family, a class of peptidic NPs with promising anticancer activities and diverse mode-of-action at the molecular level. By a combination of structure elucidation experiments, the first total synthesis of zelkovamycin and bioassays, the zelkovamycin configuration was determined and its previously proposed molecular structure was revised. The full structure assignment proves zelkovamycin as an additional member of the argyrins with however unique OXPHOS inhibitory properties. Zelkovamycin may therefore not only serve as a new starting point for chemical inhibitors of the OXPHOS system, but also guide customized argyrin NP isolation and biosynthesis studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202001577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383741PMC
July 2020

Metabolic reconstruction of the genome of candidate Desulfatiglans TRIP_1 and identification of key candidate enzymes for anaerobic phenanthrene degradation.

Environ Microbiol 2019 04 7;21(4):1267-1286. Epub 2019 Feb 7.

Biofilm Centre, Aquatic Microbiology Department, Faculty of Chemistry, University Duisburg-Essen, Essen, Germany.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed pollutants. As oxygen is rapidly depleted in water-saturated PAH-contaminated sites, anaerobic microorganisms are crucial for their consumption. Here, we report the metabolic pathway for anaerobic degradation of phenanthrene by a sulfate-reducing enrichment culture (TRIP) obtained from a natural asphalt lake. The dominant organism of this culture belongs to the Desulfobacteraceae family of Deltaproteobacteria and genome-resolved metagenomics led to the reconstruction of its genome along with a handful of genomes from lower abundance bacteria. Proteogenomic analyses confirmed metabolic capabilities for dissimilatory sulfate reduction and indicated the presence of the Embden-Meyerhof-Parnas pathway, a complete tricarboxylic acid cycle as well as a complete Wood-Ljungdahl pathway. Genes encoding enzymes putatively involved in the degradation of phenanthrene were identified. This includes two gene clusters encoding a multisubunit carboxylase complex likely involved in the activation of phenanthrene, as well as genes encoding reductases potentially involved in subsequent ring dearomatization and reduction steps. The predicted metabolic pathways were corroborated by transcriptome and proteome analyses, and provide the first insights into the metabolic pathway responsible for the anaerobic degradation of three-ringed PAHs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1462-2920.14527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849830PMC
April 2019

Identification of the Natural Product Rotihibin A as a TOR Kinase Signaling Inhibitor by Unbiased Transcriptional Profiling.

Chemistry 2018 Aug 27;24(48):12500-12504. Epub 2018 Jul 27.

Chemical Biology, Zentrum für Medizinische Biotechnologie, Universität Duisburg-Essen, Universitätsstrasse 2, 45117, Essen, Germany.

Bioactive natural products are important starting points for developing chemical tools for biological research. For elucidating their bioactivity profile, biological systems with concise complexity such as cell culture systems are frequently used, whereas unbiased investigations in more complex multicellular systems are only rarely explored. Here, we demonstrate with the natural product Rotihibin A and the plant research model system Arabidopsis thaliana that unbiased transcriptional profiling enables a rapid, label-free, and compound economic evaluation of a natural product's bioactivity profile in a complex multicellular organism. To this end, we established a chemical synthesis of Rotihibin A as well as that of structural analogues, followed by transcriptional profiling-guided identification and validation of Rotihibin A as a TOR signaling inhibitor (TOR=target of rapamycin). These findings illustrate that a combined approach of transcriptional profiling and natural product research may represent a technically simple approach to streamline the development of chemical tools from natural products even for biologically complex multicellular biological systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.201802647DOI Listing
August 2018
-->