CADM1 interacts with Tiam1 and promotes invasive phenotype of human T-cell leukemia virus type I-transformed cells and adult T-cell leukemia cells.

Abstract

CADM1 encodes a multifunctional immunoglobulin-like cell adhesion molecule whose cytoplasmic domain contains a type II PSD95/Dlg/ZO-1 (PDZ)-binding motif (BM) for associating with other intracellular proteins. Although CADM1 lacks expression in T lymphocytes of healthy individuals, it is overexpressed in adult T-cell leukemia-lymphoma (ATL) cells. It has been suggested that the expression of CADM1 protein promotes infiltration of leukemic cells into various organs and tissues, which is one of the frequent clinical manifestations of ATL. Amino acid sequence alignment revealed that Tiam1 (T-lymphoma invasion and metastasis 1), a Rac-specific guanine nucleotide exchange factor, has a type II PDZ domain similar to those of membrane-associated guanylate kinase homologs (MAGUKs) that are known to bind to the PDZ-BM of CADM1. In this study, we demonstrated that the cytoplasmic domain of CADM1 directly interacted with the PDZ domain of Tiam1 and induced formation of lamellipodia through Rac activation in HTLV-I-transformed cell lines as well as ATL cell lines. Our results indicate that Tiam1 integrates signals from CADM1 to regulate the actin cytoskeleton through Rac activation, which may lead to tissue infiltration of leukemic cells in ATL patients.

• Authors: Mari Masuda, Tomoko Maruyama, Tsutomu Ohta, Akihiko Ito, Tomayoshi Hayashi, Kunihiko Tsukasaki, Shimeru Kamihira, Shoji Yamaoka, Hiroo Hoshino, Teruhiko Yoshida, Toshiki Watanabe, Eric J Stanbridge, Yoshinori Murakami
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 20 Pg. 15511-15522 (May 14 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 20215110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CADM1 protein, human
• Cell Adhesion Molecule-1
• Cell Adhesion Molecules
• Guanine Nucleotide Exchange Factors
• Immunoglobulins
• Membrane Proteins
• RNA, Small Interfering
• T-Lymphoma Invasion and Metastasis-inducing Protein 1
• TIAM1 protein, human
• Tumor Suppressor Proteins

Topics

• Amino Acid Sequence
• Base Sequence
• Cell Adhesion Molecule-1
• Cell Adhesion Molecules
• Cell Line, Tumor
• Guanine Nucleotide Exchange Factors (chemistry, metabolism)
• Human T-lymphotropic virus 1 (pathogenicity)
• Humans
• Immunoglobulins (chemistry, metabolism)
• Immunohistochemistry
• Leukemia, T-Cell (pathology)
• Membrane Proteins (chemistry, metabolism)
• Microscopy, Confocal
• Molecular Sequence Data
• Neoplasm Invasiveness
• Protein Binding
• RNA Interference
• RNA, Small Interfering
• Sequence Homology, Amino Acid
• T-Lymphoma Invasion and Metastasis-inducing Protein 1
• Tumor Suppressor Proteins (chemistry, metabolism)