Protein modifications throughout the lung cancer proteome unravel the cancer-specific regulation of glycolysis.
Cell Rep
; 37(12): 110137, 2021 12 21.
Article
in En
| MEDLINE
| ID: mdl-34936872
ABSTRACT
Glycolytic reprogramming is a typical feature of cancer. However, the cancer-specific modulation of glycolytic enzymes requires systematic elucidation. Here, we report a range of dysregulated modifications in association with a family of enzymes specifically related to the glycolysis pathway by systematic identification of delta masses at the proteomic scale in human non-small-cell lung cancer. The most significant modification is the delta mass of 79.967 Da at serine 58 (Ser58) of triosephosphate isomerase (TPI), which is confirmed to be phosphorylation. Blocking TPI Ser58 phosphorylation dramatically inhibits glycolysis, cancer growth, and metastasis. The protein kinase PRKACA directly phosphorylates TPI Ser58, thereby enhancing TPI enzymatic activity and glycolysis. The upregulation of TPI Ser58 phosphorylation is detected in various human tumor specimens and correlates with poor survival. Therefore, our study identifies a number of cancer-specific protein modifications spanned on glycolytic enzymes and unravels the significance of TPI Ser58 phosphorylation in glycolysis and lung cancer development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triose-Phosphate Isomerase
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Protein Processing, Post-Translational
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Proteome
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Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
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Glycolysis
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Lung Neoplasms
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article
Affiliation country:
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA