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Updated: Aug 6, 2026
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Oncogene-dependent tumor suppression: using the dark side of the force for cancer therapy
G I Evan1, M Christophorou, E A Lawlor
1Cancer Research Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143-0875, USA.
Abstract:
Cancers arise by an evolutionary process that involves the protracted acquisition by somatic cells of suites of interlocking mutations that uncouple proliferation, survival, migration, and damage responses from the mechanisms (selective pressures) that normally restrain or restrict them in time and space. The relative rareness of cancer cells within the soma, in the face of huge numbers of available cell targets, substantial rates of mutation, and an abundance of proto-oncogenes and tumor suppressor gene targets, indicates that the evolutionary space available to incipient tumor cells is highly restricted. The principal way in which this is achieved is through intrinsic tumor suppression pathways-innate growth arrest and apoptotic programs that fulfill an essentially analogous functional role to checkpoints in the cell cycle machinery by antagonizing the tumorigenic potential of oncogenic mutations. Using switchable transgenic and knockin mouse models, it is possible to identify these various tumor suppressor programs and establish where, when, how, and why they act to forestall neoplasia in each tissue type and, consequently, how and why their failure leads to cancer.
Insights
Cancer develops through a complex evolutionary process where cells acquire mutations. Intrinsic tumor suppressor pathways act as crucial barriers, preventing uncontrolled cell growth and cancer formation.
Area of Science:
- Oncology
- Evolutionary Biology
- Genetics
Background:
- Cancers emerge from somatic cells acquiring mutations that disrupt normal proliferation and survival controls.
- The rarity of cancer suggests significant evolutionary constraints on tumor development.
- Intrinsic tumor suppression pathways, including growth arrest and apoptosis, counteract oncogenic mutations.
Purpose of the Study:
- To investigate the mechanisms of intrinsic tumor suppression.
- To understand how these pathways prevent neoplasia in specific tissue types.
- To elucidate how the failure of these pathways contributes to cancer.
Main Methods:
- Utilizing switchable transgenic mouse models.
- Employing knockin mouse models.
- Analyzing tumor suppressor program activity in various tissue contexts.
Main Results:
- Identified specific tumor suppressor programs.
- Determined the tissue-specific action of these programs in preventing cancer.
- Established the link between pathway failure and cancer development.
Conclusions:
- Intrinsic tumor suppression pathways are critical in preventing cancer by antagonizing oncogenic mutations.
- Understanding these pathways and their failure is key to comprehending cancer etiology.
- Mouse models are valuable tools for dissecting tumor suppression mechanisms.
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