A common stage of advanced prostate cancer is castration-resistant prostate cancer (CRPC), greater understanding of which is required in order to address and solve the clinically difficult challenge. Cathepsin K (CTSK) is a cysteine protease that usually has a strong activity of degrading extracellular matrix and is related to osteoclast-mediated bone destruction. However, the mechanism of CTSK-regulation in CRPC is still unclear to us. The current study aimed to analyze the expression of differentially expressed genes (DEGs) in patient samples (from localized PC and CRPC). Interestingly, we found that CTSK to be significantly up-regulated in CRPC. Through further signal pathway enrichment analysis, we found that the IL-17 signaling pathway to be highly correlated with CTSK. The oncogenic functions of CTSK and IL-17 in CRPC were proven by a series of in vivo and in vitro experiments. Possible downstream molecules of CTSK were investigated, which could serve as control elements to regulate the expression of EMT, thereby facilitating the metastasis and excessive proliferation of PC cells. Expression of CTSK was related to high concentration of M2 tumor-associated macrophages (TAMs) M2 in CRPC. A CTSK-mediated feedback circuit between TAMs and CRPC tissues was indicated in the process of transfer, proving the possibility of CTSK could be use as an available therapeutic target for CRPC.

Prostate cancer is a common malignant tumor, which can spread to multiple organs in the body. Metastatic disease is the dominant reason of death for patients with prostate cancer. Prostate cancer usually transfers to bone. Bone metastases are related to pathologic fracture, pain, and reduced survival. There are many known targets for prostate cancer treatment, including androgen receptor (AR) axis, but drug resistance and metastasis eventually develop in advanced disease, suggesting the necessity to better understand the resistance mechanisms and consider multi-target medical treatment. Because of the limitations of approved treatments, further research into other potential targets is necessary. Metastasis is an important marker of cancer development, involving numerous factors, such as AKT, EMT, ECM, tumor angiogenesis, the development of inflammatory tumor microenvironment, and defect in programmed cell death. In tumor metastasis, programmed cell death (autophagy, apoptosis, and necroptosis) plays a key role. Malignant cancer cells have to overcome the different forms of cell death to transfer. The article sums up the recent studies on the mechanism of bone metastasis involving key regulatory factors such as macrophages and AKT and further discusses as to how regulating autophagy is crucial in relieving prostate cancer bone metastasis.

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Objective: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer (PC) that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. In our investigation, there appeared to be a strong correlation between neuroendocrine differentiation prostate cancer (NEDPC) and NEPC. The objectives of this study included exploring whether NEDPC is an intermediate stage in the progression of high-risk prostate cancer (HRPC) to NEPC and identifying risk factors and new targets associated with survival in the treatment of NEPC.Methods: The selected prostate cancer patients were progressed to high-risk and characterized by neuroendocrine. We collected the clinical data and characteristics of patients with three types of cancer: the incidence of metastasis, site and time of metastasis, recurrence rate, related treatment methods, etc. The similarity and differences of the three groups were compared through experiment and database.Results: By analyzing the clinical data and immunohistochemical results, we found that there seems to be a clinical feature of neuroendocrine differentiation (NED) status in between when patients progress from PC to NEPC. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC. The metastasis-free survival curve and the immunohistochemical results are informing us that NEDPC can be a pre-state for diagnosing NEPC.Conclusion: NEPC is a late PC symptom that is frequently disregarded and has a bad prognosis. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC.