title: MALT1 Inhibition of Oral Carcinoma Cell Invasion and ERK/MAPK Activation.
abstract: The expression of mucosa-associated lymphoid tissue 1 (MALT1) that activates nuclear factor (NF)-κB in lymphocyte lineages is rapidly inactivated in oral carcinoma cells at the invasive front and the patients with worst prognosis. However, its mechanism to accelerate carcinoma progression remains unknown, and this study was carried out to examine the role in invasion. HSC2 oral carcinoma cells stably expressing wild-type MALT1 (wtMALT1) reduced the invasion of basement membrane matrices and collagen gels, and the dominant-negative form (∆MALT1)-expressing cells aggressively invaded into collagen gels. MALT1 decelerated proliferation and migration of cells and downregulated expression of matrix metalloproteinase 2 and 9, which were confirmed by short interfering RNA transfections. Reporter assays and immunoblot analysis showed that MALT1 does not affect the NF-κB pathway but inhibits ERK/MAPK activation. This was confirmed by endogenous MALT1 expression in oral carcinoma cell lines. Orthotopic implantation of ∆MALT1-expressing HSC2 cells in mice grew rapid expansive and invasive tongue tumors in contrast to an absence of tumor formation by wtMALT1-expressing cells. These results demonstrate that MALT1 suppresses oral carcinoma invasion by inhibiting proliferation, migration, and extracellular matrix degradation and that the ERK/MAPK pathway is a target of MALT1 and further suggests a role as a suppressor of carcinoma progression.
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Pathology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Soeno
authors.affiliation: Department of Pathology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shirako
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sudo
authors.affiliation: Division of Oral Diagnosis, Dental and Maxillofacial Radiology and Oral Pathology Diagnostic Services, Nippon Dental University Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yagishita
authors.affiliation: Department of Pathology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Taya
authors.affiliation: Department of Oral Surgery, School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kawashiri
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan kimai@tky.ndu.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D000818:Animals; D020169:Caspases / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
keywords: human MALT1 protein; matrix metalloproteinases; mitogen-activated protein kinases; mouth neoplasm; neoplasm invasiveness; squamous cell carcinoma