Copper (Cu) is an essential trace element required for mitochondrial respiration. We show that Cu drives coordinated metabolic remodeling of bioenergy, biosynthesis and redox homeostasis and promotes tumor growth and progression of clear cell renal cell carcinoma (ccRCC). Late-stage ccRCCs accumulate Cu and allocate it to cytochrome c oxidase stimulating bioenergy production. Cu induces TCA cycle-dependent oxidation of glucose and its utilization for biosynthesis of a glutathione pool that protects against H2O2 generated during mitochondrial respiration, therefore coordinating bioenergy production with redox protection. Single cell transcriptomics determined induction of mitochondrial electron transport chain, expression of NRF2 targets and glutathione biosynthesis, and decrease in HIF activity, the hallmark of ccRCC, during disease progression. Spatial transcriptomics identified that cancer cells with proliferative phenotype are embedded in clusters of cells with oxidative metabolism supporting effects of metabolic states on ccRCC progression. Our work establishes novel vulnerabilities with potential for therapeutic interventions in ccRCC.
from sddb import Catalog
cohort = Catalog().collection("geo-gse250163")
cohort.members # the 4 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse250163")
coll.ordered_artifacts.to_dataframe() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse250163 --dest data/Licenses: 4 NCBI GEO policy
@article{Bischoff_2024,
title = {Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma},
volume = {15},
ISSN = {2159-8290},
url = {http://dx.doi.org/10.1158/2159-8290.cd-24-0187},
DOI = {10.1158/2159-8290.cd-24-0187},
number = {2},
journal = {Cancer Discovery},
publisher = {American Association for Cancer Research (AACR)},
author = {Bischoff, Megan E. and Shamsaei, Behrouz and Yang, Juechen and Secic, Dina and Vemuri, Bhargav and Reisz, Julie A. and D’Alessandro, Angelo and Bartolacci, Caterina and Adamczak, Rafal and Schmidt, Lucas and Wang, Jiang and Martines, Amelia and Venkat, Jahnavi and Tcheuyap, Vanina Toffessi and Biesiada, Jacek and Behrmann, Catherine A. and Vest, Katherine E. and Brugarolas, James and Scaglioni, Pier Paolo and Plas, David R. and Patra, Krushna C. and Gulati, Shuchi and Landero Figueroa, Julio A. and Meller, Jarek and Cunningham, John T. and Czyzyk-Krzeska, Maria F.},
year = {2024},
month = Oct,
pages = {401–426}
}