Identification of annexin A13 as a regulator of chemotherapy resistance using random homozygous gene perturbation.

OBJECTIVE:To utilize a powerful new technology for target discovery, Random Homozygous Gene Perturbation (RHGP), and to identify novel targets that cause tumor cells to become chemoresistant. STUDY DESIGN:RHGP was used to identify and validate genetic changes that cause chemoresistance of tumor cells to Rapamycin. RESULTS:A series of targets was identified that allowed tumor cells to survive treatment with Rapamycin. We validated these targets and focused on Annexin A13, a target where decreased expression caused tumor cell insensitivity to Rapamycin. Ectopic overexpression of Annexin A13 was likewise sufficient to sensitize malignant breast cancer cells to treatment with Rapamycin. CONCLUSION:These findings expand our knowledge of mechanisms that allow tumor cell drug resistance and demonstrate the power of RHGP to identify novel targets and mechanisms.

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