The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone

Abstract

Backgroud:Constitutive activation of TGF-β signalling is a well-recognised mechanism in bone metastasis of prostate cancer (PCa). Protein Interacting with PRKCA 1 (PICK1) is a critical negative regulator of the TGF-β pathway. However, the clinical significance and biological role of PICK1 in PCa bone metastasis remain obscure.Methods:PICK1 expression is evaluated by immunohistochemistry (IHC) in 198 PCa patients. Statistical analysis is performed to explore correlation between PICK1 expression and clinicopathological features in PCa patients. The biological role of PICK1 is examined in PC-3 and C4-2B cells in vitro and a mouse intracardial model in vivo.Results:PICK1 expression is decreased in PCa tissues with bone metastasis and bone-derived cells and downregulation of PICK1 positively correlates with serum PSA level, Gleason grade and bone metastasis status in PCa patients. Overexpression of PICK1 suppresses PCa cell invasion and migration in vitro and bone metastasis in vivo. Our results further indicate downregulation of PICK1 is caused by miR-210-3p overexpression in PCa tissues with bone metastasis. Clinical negative correlation of PICK1 with miR-210-3p is confirmed in PCa tissues.Conclusions:Our findings uncover a novel functionally and clinically relevant epigenetic regulatory mechanism for constitutive activation of TGF-β signalling in bone metastasis of PCa.

Transcriptional downregulation of miR‐127‐3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5

“…U6 or GAPDH was used as the endogenous control. The relative fold expression of each gene was calculated with the comparative threshold cycle () method as previously described . The primers used are listed in Table S2.…”

Overexpression of SHCBP1 promotes migration and invasion in gliomas by activating the NF‐κB signaling pathway

“…GAPDH was used as an internal control. Fold changes in expression were calculated using the 2−ΔΔCt method, according to previous studies …”

SMAD3/SP1 complex‐mediated constitutive active loop between lncRNA PCAT7 and TGF‐β signaling promotes prostate cancer bone metastasis

“…Transwell assays were performed to determine the migration and invasion capability of PCa cells following the previous description (Dai et al , ). Invasion and migration assays were performed using a Transwell chamber consisting of 8‐mm membrane filter inserts (Corning, NY, USA) with or without Matrigel (BD Biosciences, Franklin Lakes, NJ, USA) coating.…”

“…Reciprocally, bone microenvironment promotes the proliferation of cancer cells through osteoblast‐producing growth factors, including TGF‐β (Weilbaecher et al , ), which leads to a vicious cycle, in which TGF‐β is a significant component. Indeed, TGF‐β signaling has been widely reported to promote bone metastasis of multiple human cancers, including PCa and breast cancer (Dai et al , ; Fournier et al , ; Kang et al , ; Korpal et al , ; Yin et al , ). Importantly, therapies targeting TGF‐β present favorable benefits for antibone metastasis treatment of cancer (Hu et al , ; Wan et al , ).…”