Inhibition of TGF-β and EGF pathway gene expression and migration of oral carcinoma cells by mucosa-associated lymphoid tissue 1

Abstract

Background:Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas.Methods:Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migratory abilities of cells in response to MALT1 were determined by wound-healing assay and time-lapse analysis.Results:Totally, 2933 genes upregulated or downregulated in MALT1-expressing cells were identified. The subsequent pathway analysis implicated the inhibition of epidermal growth factor and transforming growth factor-β signalling gene expression, and highlighted the involvement in the cellular movement. Wound closure was suppressed by wild-type MALT1 (66.4%) and accelerated by dominant-negative MALT1 (218.6%), and the velocities of cell migration were increased 0.2-fold and 3.0-fold by wild-type and dominant-negative MALT1, respectively.Conclusion:These observations demonstrate that MALT1 represses genes activating the aggressive phenotype of carcinoma cells, and suggest that MALT1 acts as a tumour suppressor and that the loss of expression stimulates oral carcinoma progression.

Proteomic identification of keratin alterations with enhanced proliferation of oral carcinoma cells by loss of mucosa-associated lymphoid tissue 1 expression

“…Expression of K5/14 is an independent risk factor for worse prognosis of oral carcinomas (31). Although a molecular mechanism for MALT1-dependent keratin alteration is uncertain, our recent microarray analysis indicated that MALT1 preferentially downregulates EGF and TGF-β pathway gene expression (32). EGF and TGF-β signaling suppress K8/18 expression and stimulate K5/14 expression, provoking proliferative and aggressive behavior of carcinoma cells (33)(34)(35)(36)(37).…”

Molecular pathways of oral cancer that predict prognosis and survival: A systematic review

“…The articles were critically evaluated based on STROBE [Figure 1], and 36 of these were considered for the review. [8910111213141516171819202122232425262728293031323334353637383940414243]…”

“…Twenty-one studies focused on genes and the associated pathways that explained the initiation, proliferation, and progression of OSCC. [101114161819202324252627282930313435373943]…”

Differential expression of fatty acid-binding proteins and pathological implications in the progression of tongue carcinoma

“…Since proteolytic degradation of the extracellular matrix releases growth factors (38), we should consider the impact of carcinoma cell-tissue interactions on the expression carefully. Furthermore, an intracellular signaling molecule, mucosa-associated lymphoid tissue 1, which suppresses the aggressive phenotype of oral carcinoma cells and is inactivated in the patients with worse prognosis directly affects FABP expression (39,40). Therefore both genetic and environmental factors provoke carcinoma cells to express FABP5.…”

“…FABP4 transports LCFAs to the nucleus, which is required for stable binding with peroxisome-proliferator-activated receptor (PPAR)-γ. PPAR-γ expression in tongue carcinomas is higher in patients with an improved prognosis (42) and the administration of a PPAR-γ agonist inhibits the development of tongue carcinoma (43). However, oral carcinoma cells showing aggressive phenotypes in vitro strongly upregulate FABP4 expression (40,44). Detailed future studies are required in order to further clarify the role of ectopic expression.…”