Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer.
Loading...
Embargo End Date
Authors
Jones, I
Dent, L
Higo, T
Roumeliotis, T
Arias Garcia, M
Shree, H
Choudhary, J
Pedersen, M
Bakal, C
Dent, L
Higo, T
Roumeliotis, T
Arias Garcia, M
Shree, H
Choudhary, J
Pedersen, M
Bakal, C
Document Type
Journal Article
Date
2023-01-25
Date Accepted
2022-12-19
Abstract
Almost all living cells maintain size uniformity through successive divisions. Proteins that over and underscale with size can act as rheostats, which regulate cell cycle progression. Using a multiomic strategy, we leveraged the heterogeneity of melanoma cell lines to identify peptides, transcripts, and phosphorylation events that differentially scale with cell size. Subscaling proteins are enriched in regulators of the DNA damage response and cell cycle progression, whereas super-scaling proteins included regulators of the cytoskeleton, extracellular matrix, and inflammatory response. Mathematical modeling suggested that decoupling growth and proliferative signaling may facilitate cell cycle entry over senescence in large cells when mitogenic signaling is decreased. Regression analysis reveals that up-regulation of TP53 or CDKN1A/p21CIP1 is characteristic of proliferative cancer cells with senescent-like sizes/proteomes. This study provides one of the first demonstrations of size-scaling phenomena in cancer and how morphology influences the chemistry of the cell.
Citation
Science Advances, 2023, 9 (4), pp. eadd0636 -
Source Title
Science Advances
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
ISSN
2375-2548
eISSN
2375-2548
2375-2548
2375-2548
Collections
Research Team
Dynamical Cell Systems
Functional Proteomics
Prote & Metabolomics Fac
Targeted Therapy
Functional Proteomics
Prote & Metabolomics Fac
Targeted Therapy