Open AccessIdentification of zinc finger protein of the cerebellum 5 as a survival factor of prostate and colorectal cancer cells
Author(s) -
Satow Reiko,
Inagaki Shota,
Kato Chiaki,
Shimozawa Makoto,
Fukami Kiyoko
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13419
Subject(s) - gene knockdown , cancer research , zinc finger , colorectal cancer , zinc finger transcription factor , prostate cancer , cancer , stat protein , biology , cell growth , cancer cell , medicine , signal transduction , transcription factor , cell culture , microbiology and biotechnology , biochemistry , genetics , stat3 , gene
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.