Mucosa-Associated Lymphoid Tissue 1 Is an Oncogene Inducing Cell Proliferation, Invasion, and Tumor Growth via the Upregulation of NF-κB Activity in Human Prostate Carcinoma Cells

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.

The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells

“…Unlike LNCaP cells, both PC-3 and DU145 cells have constitutively active NF-κB signaling [ 48 , 49 ]. Our recent study verified that MALT1 is an NF-κB-upregulated oncogene, and a positive feedback loop was found in prostate carcinoma cells [ 27 ]. In alignment with CAPE, an NF-κB signaling inhibitor, the current study proves that CAPE blocked NF-κB activity by downregulating MALT1 expression in PC-3 cells ( Figure 3 ).…”

“…The 5′-DNA fragment (−1 to −6313) of MALT1 , according to the sequence from GenBank (AP005018.1), was synthesized by Invitrogen. The human MALT1 reporter vector was constructed by cloning the DNA fragment into the pGL3-Basic reporter vector (pbGL3) (Promega Biosciences, Madison, WI, USA) with Hind III sites, as described previously [ 27 ].…”

“…The NF-κB (p65) binding activity was performed using an NF-κB (p65) Transcription Factor Assay Kit (Item No. 10007889, Cayman Chemical, Ann Arbor, MI, USA), as described previously [ 27 ]. Briefly, the nuclear extracts were incubated with consensus dsDNA sequences in each well overnight at 4 °C.…”

“…MALT1 also plays distinct roles in the progression of solid nonlymphoid tumors, including breast cancer, lung cancer, melanoma, and cholangiocarcinoma [ 23 , 24 , 25 , 26 ]. Our recent study further revealed that MALT1 activates the IKK complex to induce nuclear NF-κB accumulation in prostate carcinoma cells [ 27 ]. However, in the human prostate, whether CAPE is a MALT1 expression modulator, and the regulatory mechanisms of CAPE on MALT1, remain unclear, even though studies have indicated that CAPE downregulates NF-κB by inhibiting the translocation of NF-κB subunits into the nucleus [ 6 , 12 ].…”

The Paracaspase MALT1 in Cancer

“…Furthermore, several other studies have identified MALT1 as a central regulator of NF-κB-mediated cancer progression. Both pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (PCa) cells show increased MALT1 expression that contributes to tumor malignancy and metastasis [ 89 , 90 ]. Silencing or pharmacological inhibition of MALT1 reduces the proliferative and invasive potential of the tumor cells both in vitro and in vivo.…”