Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-5642
Authors: | Kadioglu, Onat Saeed, Mohamed Munder, Markus Spuller, Andreas Greten, Henry Johannes Efferth, Thomas |
Title: | Identification of novel rare ABCC1 transporter mutations in tumor biopsies of cancer patients |
Online publication date: | 9-Feb-2021 |
Year of first publication: | 2020 |
Language: | english |
Abstract: | The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature stop codons, and compared with the wild-type protein in terms of their protein structure. Nonsense mutations lead to truncated protein structures. Molecular docking and heat map analyses of ABCC1/MRP1 pointed out that Lys498* appeared in a separate cluster branch due to the large deletion, leading to a massive disruption in the protein conformation. The resulting proteins, which are nonfunctional due to nonsense mutations in tumors, offer a promising chemotherapy strategy since tumors with nonsense mutations may be more sensitive to anticancer drugs than wild-type ABCC1-expressing tumors. This could provide a novel tumor-specific toxicity strategy and a way to overcome drug resistance. |
DDC: | 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-5642 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Cells 9 2 |
Pages or article number: | 299 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2020 |
ISSN: | 2073-4409 |
Publisher URL: | https://doi.org/10.3390/cells9020299 |
Publisher DOI: | 10.3390/cells9020299 |
Appears in collections: | JGU-Publikationen |
Files in This Item:
File | Description | Size | Format | ||
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kadioglu_onat-identification-20210209101413928.pdf | 1.77 MB | Adobe PDF | View/Open |