Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer.
Date
2023-01-25Author
Jones, I
Dent, L
Higo, T
Roumeliotis, T
Arias Garcia, M
Shree, H
Choudhary, J
Pedersen, M
Bakal, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Proteome
Melanoma
Cell Cycle
Cell Line
Cell Proliferation
Cellular Senescence
Research team
Dynamical Cell Systems
Functional Proteomics
Prote & Metabolomics Fac
Targeted Therapy
Language
eng
Date accepted
2022-12-19
License start date
2023-01-25
Citation
Science Advances, 2023, 9 (4), pp. eadd0636 -
Publisher
AMER ASSOC ADVANCEMENT SCIENCE