Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer

Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.

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SPP1 Promotes Enzalutamide Resistance and EMT Activation in CRPC Progression via PI3K/AKT and ERK1/2 Pathways

10.21203/rs.3.rs-533801/v1 ◽

2021 ◽

Author(s):

Xiaocong Pang ◽

Junling Zhang ◽

Xu He ◽

Yanlun Gu ◽

Wei Yu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Epithelial Mesenchymal Transition ◽

Strong Relationship ◽

Castration Resistant Prostate Cancer ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Castration Resistant ◽

And Migration

Abstract The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and anti-androgen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, metastatic levels in CRPC progression, and also investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity, and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, PCR, immunohistochemical staining and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC. SPP1 knockdown repressed enzalutamide sensitivity, invasion and migration of prostate cancer cells in vitro. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrate that SPP1 overexpression maintains the activation of PI3K/AKT signaling and ERK1/2 pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression, and help to discover new potential targets against mCRPC.

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