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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.