Abstract

Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue 1 (MALT1) is a novel gene involved in nuclear factor κB (NF-κB) signal transduction by acting as an adaptor protein and paracaspase, with an essential role in inflammation and tumorigenesis in many cancers. This study investigated the functions and the potential regulatory mechanisms of MALT1 in the human prostate cancer cells. We found that MALT1 is abundant in prostate cancer tissues. MALT1 facilitated NF-κB subunits (p50 and p65) nuclear translocation to induce gene expression of interleukin 6 (IL-6) and C-X-C motif chemokine 5 (CXCL5) in prostate carcinoma cells. MALT1 promoted cell proliferation, invasion, and tumor growth in vitro and in vivo. MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells.

Highlights

  • Prostate cancer (PCa) is the most frequently diagnosed malignancy and the sixth most common cause of cancer-related death in the world

  • To determine the correlation between Mucosa-associated lymphoid tissue 1 (MALT1) gene expression and metastasis in prostate cancer, the expression levels of MALT1 were characterized in five types of prostate cells

  • The present study showed that metastatic prostate carcinoma cells (LNCaP, PC-3, and DU145) have higher MALT1 expression compared to non-metastatic cells (PZ-HPV-7 and CA-HPV-10), and MALT1 is abundant in advanced prostate cancerous tissues, suggesting that MALT1 could be an oncogene in the human prostate

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Summary

Introduction

Prostate cancer (PCa) is the most frequently diagnosed malignancy and the sixth most common cause of cancer-related death in the world. The androgen deprivation therapy provides only a transient control for recurrent prostate cancer that may result in progression from hormone-sensitive to aggressive castration-resistant PCa (CRPC). Androgen independence characterized by a resistance to such therapy [3]. It is needed to find the novel mechanisms related to the PCa progression, especially to those who are androgen-independent. The nuclear factor κB (NF-κB) pathways is regarded as a link between inflammation and progression of certain types of cancer, including PCa [4,5,6].

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