Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Fukuhara, Hiroshi; Masvuda, Mari; Sakurai-Yageta, Mika; Fukami, Takeshi; Kuramochi, Masami; Maruyama, Tomoko; Kitamura, Tadaichi; Murakami, Yoshinori

doi:10.1038/sj.onc.1206744

Cited by 71 publications

(60 citation statements)

References 27 publications

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“…We have demonstrated that protein4.1B/DAL-1, a member of the protein 4.1 family, connects TSLC1 to the actin cytoskeleton, and the interaction is involved in actin reorganization (9). Along with others, we have reported that TSLC1 also interacts with membrane-associated guanylate kinase homologs (MAGuKs) through its class II PDZ domain (6,7,10), implying that TSLC1, protein 4.1, and MAGuK form a tripartite complex. TSLC1 was originally identified based upon its ability to suppress tumorigenicity of human lung adenocarcinoma A549 cells in nude mice (2).…”

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confidence: 54%

Tumor Suppressor in Lung Cancer (TSLC)1 Suppresses Epithelial Cell Scattering and Tubulogenesis

Masuda¹,

Kikuchi²,

Maruyama³

et al. 2005

Journal of Biological Chemistry

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confidence: 54%

Tumor Suppressor in Lung Cancer (TSLC)1 Suppresses Epithelial Cell Scattering and Tubulogenesis

Masuda¹,

Kikuchi²,

Maruyama³

et al. 2005

Journal of Biological Chemistry

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“…Furthermore, the intracellular tails of the Cadms have been shown to interact with several scaffolding molecules in various in vitro systems. These include CASK (Biederer et al, 2002), syntenin (Biederer et al, 2002;Meyer et al, 2004), GRIP (Meyer et al, 2004), MPP3 (ortholog of the Drosophila tumor suppressor gene Dlg; Fukuhara et al, 2003), and DAL-1 (Yageta et al, 2002). However, very little is known about how these interactions relate to the functions of the Cadms during development.…”

Section: Introductionmentioning

confidence: 99%

Six cadm/synCAM genes are expressed in the nervous system of developing zebrafish

Pietri

Easley-Neal

Wilson

et al. 2007

Developmental Dynamics

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The Cadm (cell adhesion molecule) family of cell adhesion molecules (also known as IGSF4, SynCAM, Necl and TSLC) has been implicated in a multitude of physiological and pathological processes, such as spermatogenesis, synapse formation and lung cancer. The precise mechanisms by which these adhesion molecules mediate these diverse functions remain unknown. To investigate mechanisms of action of these molecules during development, we have identified zebrafish orthologs of Cadm family members and have examined their expression patterns during development and in the adult. Zebrafish possess six cadm genes. Sequence comparisons and phylogenetic analysis suggest that four of the zebrafish cadm genes represent duplicates of two tetrapod Cadm genes, whereas the other two cadm genes are single orthologs of tetrapod Cadm genes. All six zebrafish cadms are expressed throughout the nervous system both during development and in the adult. The spatial and temporal patterns of expression suggest multiple roles for Cadms during nervous system development. Developmental Dynamics 237:233-246, 2008.

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“…The juxtamembrane region of the cytoplasmic tail contains a band 4.1-binding motif and binds the tumor suppressor DAL-1, a band 4.1 family member, which connects Necl-2 to the actin cytoskeleton (23). In addition, the cytoplasmic tail contains a PDZ domain-binding motif in its C-terminal region and binds Pals2, Dlg3/MPP3, and CASK, which are MAGUK subfamily members having an L27 domain (15,20,24,25). However, the exact roles of the binding of these molecules to Necl-2 remain unknown.…”

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confidence: 99%

Silencing of ErbB3/ErbB2 Signaling by Immunoglobulin-like Necl-2

Kawano

Ikeda²,

Kishimoto

et al. 2009

Journal of Biological Chemistry

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ErbB2 and ErbB3, members of the EGF receptor/ErbB family, form a heterodimer upon binding of a ligand, inducing the activation of Rac small G protein and Akt protein kinase for cell movement and survival, respectively. The enhanced ErbB3/ ErbB2 signaling causes tumorigenesis, invasion, and metastasis. We found here that the ErbB3/ErbB2 signaling is regulated by immunoglobulin-like Necl-2, which is down-regulated in various cancer cells and serves as a tumor suppressor. The extracellular region of ErbB3, but not ErbB2, interacted in cis with that of Necl-2. This interaction reduced the ligand-induced, ErbB2-catalyzed tyrosine phosphorylation of ErbB3 and inhibited the consequent ErbB3-mediated activation of Rac and Akt, resulting in the inhibition of cancer cell movement and survival. These inhibitory effects of Necl-2 were mediated by the protein-tyrosine phosphatase PTPN13 which interacted with the cytoplasmic tail of Necl-2. We describe here this novel mechanism for silencing of the ErbB3/ErbB2 signaling by Necl-2.ErbB2 and ErbB3 are members of the EGF receptor/ErbB family, which has ErbB1 and ErbB4 as additional members (1). ErbB2 and ErbB3 are also known as HER2/Neu and HER3, respectively. No ligands binding directly to ErbB2 have been identified yet, whereas heregulin (HRG) 3 -␣ and -␤, also known as neuregulin-1 and -2, respectively, directly bind to ErbB3. ErbB2 and ErbB3 have kinase domains in their cytoplasmic tails, but that of ErbB3 lacks kinase activity. Therefore, the homodimer of ErbB3 formed by binding of HRG does not transduce any intracellular signaling. By contrast, ErbB2 heterophilically interacts in cis with HRG-occupied ErbB3 and phosphorylates nine tyrosine residues of ErbB3, causing recruitment and activation of the p85 subunit of phosphoinositide 3-kinase (PI3K) and the subsequent activation of Rac small G protein and Akt protein kinase (2). The activation of Rac enhances cell movement and that of Akt prevents cell apoptosis (3).ErbB2 serves as an oncogenic protein (4), and amplification of the ErbB2 gene is observed in many types of cancers. For instance, it is amplified in ϳ3% of lung cancers, ϳ30% of breast cancers, ϳ20% of gastric cancers, and ϳ60% of ovarian cancers (5). Moreover, mutation of the ErbB2 gene is found in many types of cancers, namely, ϳ10% of lung cancers, ϳ4% of breast cancers, ϳ5% of gastric cancers, and ϳ3% of colorectal cancers (6). This gene amplification or mutation causes enhanced signaling for cell movement and survival, eventually resulting in tumorigenesis, invasiveness, and metastasis. On the basis of these properties of ErbB2, it has been recognized as a good target for cancer therapy; indeed, ErbB2-targeting drugs have already been developed and used clinically (7,8). However, it remains unknown whether ErbB2 is involved in oncogenesis in cancers in which its gene is not amplified or mutated. In addition, it was recently reported that overexpression of ErbB3 is also involved in tumor malignancy (9), but it remains unknown how ErbB3 serves as an oncogenic p...

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Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Cited by 71 publications

References 27 publications

Tumor Suppressor in Lung Cancer (TSLC)1 Suppresses Epithelial Cell Scattering and Tubulogenesis

Tumor Suppressor in Lung Cancer (TSLC)1 Suppresses Epithelial Cell Scattering and Tubulogenesis

Six cadm/synCAM genes are expressed in the nervous system of developing zebrafish

Silencing of ErbB3/ErbB2 Signaling by Immunoglobulin-like Necl-2

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