Tsui Ke-Hung, Chang Kang-Shuo, Sung Hsin-Ching, Hsu Shu-Yuan, Lin Yu-Hsiang, Hou Chen-Pang, Yang Pei-Shan, Chen Chien-Lun, Feng Tsui-Hsia, Juang Horng-Heng
Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan.
Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan.
Biomedicines. 2021 Mar 3;9(3):250. doi: 10.3390/biomedicines9030250.
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.
前列腺癌是最常见的恶性肿瘤之一,也是男性癌症相关死亡的主要原因。鉴于早期诊断和治疗的重要性,值得确定一种潜在的前列腺癌新型治疗靶点。黏膜相关淋巴组织1(MALT1)是一种新型基因,作为衔接蛋白和类半胱天冬酶参与核因子κB(NF-κB)信号转导,在许多癌症的炎症和肿瘤发生中起重要作用。本研究调查了MALT1在人前列腺癌细胞中的功能及潜在调控机制。我们发现MALT1在前列腺癌组织中含量丰富。MALT1促进NF-κB亚基(p50和p65)核转位,以诱导前列腺癌细胞中白细胞介素6(IL-6)和C-X-C基序趋化因子5(CXCL5)的基因表达。MALT1在体外和体内均促进细胞增殖、侵袭及肿瘤生长。MALT1增强前列腺癌细胞中的NF-κB活性;此外,报告基因和免疫印迹分析确定NF-κB诱导MALT1表达,这意味着MALT1和NF-κB之间存在正反馈回路。总之,MALT1是人类前列腺癌细胞中NF-κB诱导的致癌基因。