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

T Chiba1, Y Soeno2, Y Shirako2

  • 1Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.

Journal of Dental Research
|December 25, 2015
PubMed

Insights

Mucosa-associated lymphoid tissue 1 (MALT1) suppresses oral carcinoma invasion by inhibiting cell proliferation, migration, and matrix degradation. MALT1 targets the ERK/MAPK pathway, acting as a suppressor of oral cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Mucosa-associated lymphoid tissue 1 (MALT1) is crucial for NF-κB activation in lymphocytes.
  • MALT1 expression is reduced in oral carcinoma at the invasive front, correlating with poor prognosis.
  • The precise mechanism by which MALT1 influences oral cancer progression remains unclear.

Purpose of the Study:

  • To investigate the role of MALT1 in oral carcinoma invasion and progression.
  • To elucidate the molecular pathways targeted by MALT1 in oral cancer cells.

Main Methods:

  • Stable expression of wild-type (wtMALT1) and dominant-negative (∆MALT1) MALT1 in HSC2 oral carcinoma cells.
  • Invasion assays using basement membrane matrices and collagen gels.
  • Short interfering RNA (siRNA) transfections to confirm gene downregulation.
  • Reporter assays and immunoblot analysis to assess pathway activation.
  • Orthotopic implantation of modified cells in mouse models.

Main Results:

  • wtMALT1 expression reduced cell invasion, proliferation, and migration.
  • ∆MALT1 expression led to aggressive invasion into collagen gels.
  • MALT1 downregulated matrix metalloproteinase 2 and 9 (MMP2/9) expression.
  • MALT1 inhibited ERK/MAPK activation, independent of the NF-κB pathway.
  • In vivo studies showed wtMALT1 suppressed tumor formation, while ∆MALT1 promoted rapid, invasive tumor growth.

Conclusions:

  • MALT1 acts as a suppressor of oral carcinoma invasion and progression.
  • MALT1 inhibits proliferation, migration, and extracellular matrix degradation.
  • The ERK/MAPK pathway is a key target inhibited by MALT1 in oral cancer.

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