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Interleukin-6/signal transducer and activator of transcription 3 promotes
prostate cancer resistance to androgen deprivation therapy via regulating
pituitary tumor transforming gene 1 expression
#MMPMID29288516
Huang S
; Liu Q
; Liao Q
; Wu Q
; Sun B
; Yang Z
; Hu X
; Tan M
; Li L
Cancer Sci
2018[Mar]; 109
(3
): 678-687
PMID29288516
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Prostate cancer can progress from androgen dependence to androgen deprivation
resistance with some unknown mechanisms. The current study aims to explore the
possible role of pituitary tumor transforming gene1 (PTTG1) in
castration-resistant prostate cancer (CRPC). Initially, we found that PTTG1
expression was significantly increased in androgen-independent prostate cancer
cell lines PC3, DU145 and CRPC specimens compared with that in androgen-dependent
prostate cancer cell line LNCaP and initial prostate cancer specimens. PTTG1
overexpression significantly enhanced the cell survival rate, clonality and
tumorigenicity in LNCaP cells upon androgen-deprivation therapy (ADT). While
knockdown of PTTG1 expression significantly elevated the sensitivity of DU145
cells to ADT. The effects of PTTG1 overexpression on LNCaP cells may be ascribed
to the induced EMT and increased CD44(+) CD24(-) cancer stem cell population.
Furthermore, we detected that PTTG1 expression was regulated by interleukin-6 via
activated signal transducer and activator of transcription 3 (STAT3) directly
binding to the region -500 to +1 of PTTG1 promoter in LNCaP cells. In conclusion,
our results elucidate that interleukin-6/STAT3 activation can increase PTTG1
expression and, consequently, promote the resistance to ADT in CRPC by inducing
EMT and increasing the cancer stem cell population, suggesting that PTTG1 may be
a novel therapeutic target for CRPC.
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