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Series GSE251905 Query DataSets for GSE251905
Status Public on Jun 17, 2024
Title Mitochondrial complex I promotes kidney cancer metastasis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Most kidney cancers display metabolic dysfunction but how this relates to cancer progression in humans is unknown. We infused 13C-labeled nutrients during surgical tumour resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic cultures ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with measurements of respiration in mitochondria isolated from kidneys and tumours, reveal electron transport chain (ETC) defects in ccRCC. However, ccRCC metastases unexpectedly have enhanced TCA cycle labeling compared to primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, while inhibiting ETC complex I decreases metastasis. These findings indicate that metabolic properties and liabilities evolve during kidney cancer progression in humans, and that mitochondrial function is limiting for metastasis but not for growth at the original site.
 
Overall design RNA Sequencing of kidney cancer patient tissue samples. Patient samples are de-identified and are either from the adjacent kidney, a kidney cancer primary tumor, or clear cell renal cell carcinoma (ccRCC) metastasis.
 
Contributor(s) Bezwada D, DeBerardinis R
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Submission date Dec 22, 2023
Last update date Jun 17, 2024
Contact name Divya Bezwada
E-mail(s) divya.bezwada@utsouthwestern.edu, dbezwada@scripps.edu
Organization name University of Texas Southwestern Medical Center
Lab Ralph DeBerardinis, MD, PhD
Street address 5323 Harry Hines Blvd
City Dallas
State/province Texas
ZIP/Postal code 75390
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (123)
GSM7989709 VM29 Adjacent Kidney
GSM7989710 VM51 Adjacent Kidney
GSM7989711 VM60 Adjacent Kidney
Relations
BioProject PRJNA1055903

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE251905_Extended_Data_Table_2.xlsx 16.0 Mb (ftp)(http) XLSX
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Raw data are available in SRA

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