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Updated: Jul 17, 2026
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Published on: September 13, 2022
Large scale genetic screen identifies MAP17 as protein bypassing TNF-induced growth arrest
M V Guijarro1, M E Castro, L Romero
1Experimental Therapeutics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
Abstract:
Although activated macrophages destroy cancer cells more effectively than normal cells, the ability to escape activated macrophages is a characteristic of tumor cells. One of the mechanisms responsible for the specific killing of tumor cells by macrophages is the production of the cytokine tumor necrosis factor (TNF) alpha. Therefore, resistance to TNF may provide such cancer cells a selective advantage against host elimination. With the aim of identifying genes with these properties we undertook a large scale genetic screen to identify genes able to bypass TNF-induced G1 arrest. We identified MAP17, a small 17 kDa nonglycosylated membrane protein that localizes to the plasma membrane and the Golgi apparatus. Ectopic expression of MAP17 in tumor cells prevents TNF-induced G1 arrest by impairing p21waf1 induction. However, expression of MAP17 does not inhibit TNF-induced apoptosis in Me180-sensitive tumor cells. The inhibition of TNF is specific since MAP17 does not alter the response to other cytokines such as IFNgamma. As described in the Xenopus oocyte system, MAP17 increases the uptake of mannose in some cells, but this effect is not responsible for TNF bypass. We have also analyzed the expression of MAP17 mRNA in a panel of cell lines. MAP17 is expressed in 30% of cell lines of different origin. However, MAP17 mRNA expression did not correlate with TNF resistance. Our data indicates that although MAP17 expression might bypass TNF-induced growth arrest, it is not the only determinant of this response.
Insights
Tumor cells can escape activated macrophages by resisting tumor necrosis factor (TNF)-alpha. Researchers identified MAP17 as a protein that can bypass TNF-induced growth arrest in cancer cells.
Area of Science:
- Cancer Biology
- Immunology
- Molecular Biology
Background:
- Activated macrophages eliminate cancer cells via tumor necrosis factor (TNF)-alpha.
- Tumor cells often develop resistance to TNF, enabling survival and proliferation.
- Understanding resistance mechanisms is crucial for developing effective cancer therapies.
Purpose of the Study:
- To identify genes that confer resistance to TNF-induced cell cycle arrest.
- To investigate the role of the MAP17 protein in TNF resistance.
- To explore the mechanism by which MAP17 affects TNF signaling.
Main Methods:
- Large-scale genetic screening to identify genes bypassing TNF-induced G1 arrest.
- Ectopic expression of MAP17 in tumor cells.
- Analysis of p21waf1 induction and TNF-induced apoptosis.
- Assessment of MAP17's effect on other cytokine responses (IFNgamma).
- Investigation of mannose uptake and MAP17 mRNA expression in cell lines.
Main Results:
- MAP17 was identified as a gene that bypasses TNF-induced G1 arrest.
- Ectopic MAP17 expression inhibits p21waf1 induction, preventing TNF-induced growth arrest.
- MAP17 does not inhibit TNF-induced apoptosis or affect responses to other cytokines like IFNgamma.
- MAP17's effect on mannose uptake is not responsible for TNF bypass.
- MAP17 mRNA expression did not consistently correlate with TNF resistance in tested cell lines.
Conclusions:
- MAP17 can mediate resistance to TNF-induced growth arrest in tumor cells.
- MAP17's role in TNF resistance is specific and does not affect apoptosis or other cytokine pathways.
- While MAP17 contributes to bypassing TNF-induced growth arrest, it is not the sole determinant of TNF resistance.
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