Repository logo
 

Tumor diversity and the trade-off between universal cancer tasks.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Szekely, Pablo 
Bar, Noam 
Zimmer, Anat 
Sheftel, Hila 

Abstract

Recent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory, using the fact that tumors need to perform multiple tasks that contribute to their fitness. We find that trade-offs between tasks constrain tumor gene-expression to a continuum bounded by a polyhedron whose vertices are gene-expression profiles, each specializing in one task. We find five universal cancer tasks across tissue-types: cell-division, biomass and energy, lipogenesis, immune-interaction and invasion and tissue-remodeling. Tumors that specialize in a task are sensitive to drugs that interfere with this task. Driver, but not passenger, mutations tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a framework of tumor diversity grounded in evolutionary theory.

Description

Keywords

Cell Division, Energy Metabolism, Gene Expression, Humans, Lipogenesis, Mutation, Neoplasm Invasiveness, Neoplasms, Systems Biology, Tumor Escape

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
European Research Council (694620)