Analysis of the sensitization of cancer cells to DNA damaging agents by SLFN11.

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CELLBIO-10

* FARE Award Winner

Authors

• E Leo
• G Zoppoli
• M Regairaz
• W Reinhold
• Y Pommier

Abstract

To identify genes that, at the expression level, could predict the cytotoxicity profiles of antiproliferative agents in the NCI-60, we correlated the expression profile of genes in treated and untreated cells, finding that a single gene, SLFN11, showed high correlation with most classes of the DNA damaging agents (DDA). To test the relationship between SLFN11 and the sensitivity to DDAs, we silenced SLFN11 in four cells lines and tested them with different drug treatments. We found that their response to DDAs was greatly affected by the presence/absence of SLFN11, whereas it did not change the response after treatment with other classes of chemotherapeutic agents. To elucidate the function of this protein we studied survival, cell cycle, DNA replication, DNA damage and transcription in cells upon knockdown of SLFN11 and CPT treatments, finding remarkable differences in the way cells responded. In conclusion, the identification of SLFN11 modulating effects towards response to DDAs lays the ground for the study of a previously unexplored player of cell response to the most used classes of anticancer drugs. Moreover, SLFN11 could become an invaluable biomarker/predictor for the response of human cancers to chemotherapeutical regimens.

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