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

Abstract

Progression of oral carcinomas associates with aberrant activation and inactivation of molecules that work in established or unknown pathways. Although mucosa‑associated lymphoid tissue 1 (MALT1) expressed in normal oral epithelium is inactivated in the aggressive subset of carcinomas with worse prognosis, phenotypic changes of carcinoma cells upon the loss of expression is unknown. We performed a proteomic analysis to identify MALT1‑regulated proteins in oral carcinoma cells. Four different keratins were included in the ten most abundantly changed proteins. K8/18 were upregulated in MALT1 stably‑expressing carcinoma cells and K5/14 in MALT1‑marginal control cells. K8/18 upregulation and K5/14 downregulation were MALT1 dose‑dependent and observed in a series of oral carcinoma cells. MALT1 suppressed cell proliferation (0.52-fold, P<0.01) and its dominant-negative form stimulated it (1.33-fold, P<0.01). The decreased proliferation associated with reduction of cyclin D1, which was recovered by the short interfering RNA against MALT1. Taken together, loss of MALT1 expression alters keratin expression and enhances proliferation of carcinoma cells, and may progress oral carcinomas into the advanced state.

MALT1 Inhibition of Oral Carcinoma Cell Invasion and ERK/MAPK Activation

“…The wtMALT1 HSC2 cells decelerated proliferation compared to mock HSC2 cells, and it was supported by the slow proliferation of endogenous MALT1-positive cells. This is consistent with cyclin D1 expression, which is almost terminated in wtMALT1 HSC2 cells (Kawamoto et al 2013). With respect to migration, a previous study demonstrated velocities of singlecell migration ( wtMALT1 HSC2 cells, 0.21 ± 0.01 µm/h; mock HSC2 cells, 1.01 ± 0.05 µm/h; Ohyama et al 2013).…”

“…Loss of MALT1 expression in oral carcinomas is associated with a worse patient prognosis (Chiba et al 2009) and stimulates proliferation and migration of carcinoma cells (Kawamoto et al 2013;Ohyama et al 2013). However, its involvement in carcinoma invasion, which is a prime determinant of the progression, is not defined.…”

“…Cells were seeded on E-plates for the proliferation assay (1 × 10 4 cells/well) installed on the xCELLigence RTCA-DP analyzer and monitored proliferated cells (Kawamoto et al 2013).…”

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

“…Our previous study demonstrated that mucosa-associated lymphoid tissue 1 (MALT1) is expressed in the nucleus of oral epithelial cells (Chiba et al , 2009) and substitutes keratins depending on its expression (Kawamoto et al , 2013). The advanced carcinomas inactivate MALT1 expression by the promoter methylation, and the loss of expression worse the patient prognosis (Chiba et al , 2009).…”

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

“…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.…”