Overexpression of the potential kinase serine/ threonine/tyrosine kinase 1 (STYK 1) in castration-resistant prostate cancer.
Despite high response rates and clinical benefits, androgen ablation often fails to cure advanced or relapsed prostate cancer because castration-resistant prostate cancer (CRPC) cells inevitably emerge. CRPC cells not only grow under castration, but also behave more aggressively, indicating that a number of malignant signaling pathways are activated in CRPC cells as well as androgen receptor signaling. Based on information from the gene expression profiles of clinical CRPC cells, we here identified one overexpressed gene, serine/threonine/tyrosine kinase 1 (STYK1), encoding a potential kinase, as a molecular target for CRPC. RNA and immunohistochemical analyses validated the overexpression of STYK1 in prostate cancer cells, and its expression was distinct in CRPC cells. Knockdown of STYK1 by siRNA resulted in drastic suppression of prostate cancer cell growth and, concordantly, enforced expression of STYK1 promoted cell proliferation, whereas ectopic expression of a kinase-dead mutant STYK1 did not. An in vitro kinase assay using recombinant STYK1 demonstrated that STYK1 could have some potential as a kinase, although its specific substrates are unknown. These findings suggest that STYK1 could be a possible molecular target for CRPC, and small molecules specifically inhibiting STYK1 kinase could be a possible approach for the development of novel CRPC therapies.
Chung
Suyoun
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tamura
Kenji
K
Furihata
Mutsuo
M
Uemura
Motohide
M
Daigo
Yataro
Y
Nasu
Yasutomo
Y
Miki
Tsuneharu
T
Shuin
Taro
T
Fujioka
Tomoaki
T
Nakamura
Yusuke
Y
Nakagawa
Hidewaki
H
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000628:therapy; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D020794:Receptor Protein-Tyrosine Kinases; C482299:STYK1 protein, human