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Identification of specific drug targets is very important for cancer therapy. We recently identified zinc finger protein of the cerebellum 5 ( ZIC 5) as a factor that promotes melanoma aggressiveness by platelet‐derived growth factor D ( PDGFD ) expression. However, its roles in other cancer types remain largely unknown. Here we determined the roles of  ZIC 5 in prostate cancer ( PC a) and colorectal cancer ( CRC ) cells. Results showed that  ZIC 5 was highly expressed in  CRC  and dedifferentiated  PC a tissues, whereas little expression was observed in relevant normal tissues. Knockdown of  ZIC 5 decreased proliferation of several  PC a and  CRC  cell lines with induction of cell death.  ZIC 5 knockdown significantly suppressed  PDGFD  expression transcriptionally, and  PDGFD  suppression also decreased proliferation of  PC a and  CRC  cell lines. In addition, suppression of  ZIC 5 or  PDGFD  expression decreased levels of phosphorylated focal adhesion kinase ( FAK ) and signal transducer and activator of transcription 3 ( STAT 3) which are associated with  PC a and  CRC  aggressiveness. Furthermore, knockdown of  ZIC 5 or  PDGFD  enhanced death of  PC a and  CRC  cells induced by the anti‐cancer drugs docetaxel or oxaliplatin, respectively. These results suggest that  ZIC 5 and  PDGFD  promote survival of  PC a and  CRC  cells by enhancing  FAK  and  STAT 3 activity, and that the roles of  ZIC 5 are consistent across several cancer types.

Identification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells