MALT1-responsive keratin rearrangement and proliferation of oral carcinoma cells

Method: Seven oral carcinoma cell lines derived from different sites were used: oral floor, HSC2, KOSC2 and Ho1u1; tongue, HSC3 and OSC19; and gingiva, TSU and Ca9.22. HSC2 cells stably expressing full-length wild-type MALT1 (_wtMALT1HSC2 cells), the N-terminus-deleted dominant-negative form used of MALT1 ( _DMALT1HSC2 cells) or vector alone (_mockHSC2 cells) were used. Proteins that were differential expressed in _wtMALT1HSC2 cells and _mockHSC2 cells were subjected to the proteomic analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and analysed using the MASCOT database. For proliferation , the real-time cell electronic sensing assay based on electrical impedance readings in cell monolayers plated in wells containing built-in gold electrodes was performed.  

Result: The _wtMALT1HSC2 cells up-regulated K8 and K18, whereas _mockHSC2 cells expressed K5 and K14.  K8/18 was dose-dependently up-regulated and K5/14 was down-regulated by MALT1 cDNA. The K5/14-positive _DMALT1HSC2 cells enhanced the proliferation, and the K8/18-positive _wtMALT1HSC2 cells strongly decreased the proliferation with inhibiton of cyclin D1 expression, which was recovered by the siRNA for MALT1. 

Conclusion: The present study demonstrated that loss of MALT1 expression rearranges  keratin filament organization and stimulates proliferation of carcinoma cells, and suggests a suppressing role of MALT1 in oral carcinoma progression.