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

Masuda, Mari; Kikuchi, Shinji; Maruyama, Tomoko; Sakurai-Yageta, Mika; Williams, Yuko; Ghosh, Hara P.; Murakami, Yoshinori

doi:10.1074/jbc.m507136200

Cited by 35 publications

(36 citation statements)

References 24 publications

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“…Our in vitro and in vivo results suggest that the effect of Necl2 overexpression was due to reduced cell proliferation and migration, correlating with enhanced adherens junction stability and maintenance of CASK expression (Ojeh et al, 2008). Our results are consistent with previous studies which demonstrate that Necl2 overexpression in kidney cells suppresses HGF-dependent cell scattering and motility because of retention of E-cadherin-based intercellular adhesion (Masuda et al, 2005).…”

Section: Discussionsupporting

confidence: 83%

“…Studies in various tissues and cell types indicate that Necl2 expression influences epithelial cell scattering, proliferation and differentiation (Ito et al, 2007;Ito et al, 2003;Mao et al, 2003;Masuda et al, 2005;Shingai et al, 2003). Necl2 mediates homotypic intercellular adhesion and heterotypic adhesion via nectin-3, Necl1 and class I-restricted T-cell-associated molecule (CRTAM) (Galibert et al, 2005;Takai et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Necl2 mediates homotypic intercellular adhesion and heterotypic adhesion via nectin-3, Necl1 and class I-restricted T-cell-associated molecule (CRTAM) (Galibert et al, 2005;Takai et al, 2008). Necl2 has been shown to enhance E-cadherin-dependent adherens junction stability and directly interact with actin-binding proteins to regulate cytoskeletal organisation and Rho GTPase activity (Masuda et al, 2005). The cytoplasmic PDZ domain of Necl2 binds membraneassociated guanylate kinase (MAGuK) proteins including CASK, MPP3, Pals2 and syntenin (Takai et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Necl2 regulates epidermal adhesion and wound repair

et al. 2009

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Differential expression of cell adhesion molecules regulates stem cell location, self-renewal and lineage selection under steady state conditions and during tissue repair. We show that the intercellular adhesion protein nectin-like molecule 2 (Necl2) is highly expressed in bulge stem cells of adult human and mouse hair follicles. Overexpression of Necl2 in cultured human keratinocytes led to upregulation of calcium/calmodulin-associated Ser/Thr kinase (CASK), increased calcium-independent intercellular adhesion, and inhibition of cell motility and in vitro wound healing. Although the rate of cell proliferation was reduced, terminal differentiation was unaffected. To assess the role of Necl2 in vivo, we examined the epidermis of Necl2-null mice and developed transgenic mice that expressed Necl2 in the basal layer of murine epidermis. Necl2 overexpression led to a reduction in S-phase cells and an increase in quiescent cells retaining DNA label in the bulge. Although epidermal homeostasis appeared normal in both transgenic and knockout mice, wound healing was markedly delayed. Necl2 overexpression resulted in reduced proliferation and increased levels of CASK and E-cadherin at the leading edge of healing wounds, consistent with its effects in culture. Our results demonstrate that Necl2 is involved in regulating epidermal stem cell quiescence and location.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Necl2 regulates epidermal adhesion and wound repair

et al. 2009

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“…CADM1 has an important role in tumor development through suppressing epithelial-mesenchymal transition and oncogenic signaling (23). In addition to the current study which demonstrates the loss of CADM1 and CADM4 are associated with breast cancer progression, a recent study revealed that loss of CADM1 expression was detected in patients with metastasis compared with those without, suggesting that CADM1 may serve an important role in preventing the progression of metastasis (22).…”

Section: Discussionmentioning

confidence: 83%

Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer

et al. 2017

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Abstract. Cell adhesion molecule (CADM) genes encode immunoglobulin superfamily molecules, which are involved in cell-cell adhesion in a number of human epithelia. Through the maintenance of epithelia, CADM genes protect against malignant conversion and metastasis. Whilst numerous in vitro studies have investigated the molecular characteristics of CADM1 and CADM4 and in vivo studies have investigated CADM1 and CADM4 expression in a number of tumor types, the roles of CADM1 and CADM4 have yet to be elucidated. Therefore, in the present study, CADM1 and CADM4 expression levels were evaluated using immunohistochemistry staining in 208 patients with breast cancer and compared with clinicopathological factors. CADM1 and CADM4 expression levels were negative in 160 (76.9%) and 166 (79.8%) of the 208 cases, respectively. The lack of expression in these cases was associated with advanced tumor stage, suggesting that inactivation of CADM1 and CADM4 promotes breast cancer development. The prognostic role of CADM1 and CADM4 in breast cancer was also evaluated and the expression of CADM1 and CADM4 were not associated with cancer-specific survival or overall survival rate in the cohort of patients in the present study. Whilst these results suggested that CADM1 and CADM4 possess tumor suppressive roles, further functional experiments are required to address the important mechanisms involving CADM1 and CADM4.

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“…Cell scattering was quantified counting cells detached from colonies vs the total number of cells in random images as described in Masuda et al (2005).…”

Section: Scattering Assaymentioning

confidence: 99%

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

et al. 2011

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Scaffold proteins form multiprotein complexes that are central to the regulation of intracellular signaling. The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is highly expressed at the plasma membrane of normal biliary epithelial cells and binds epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with oncogenic properties. This study investigated EBP50-EGFR interplay in biliary cancer. We report that in a collection of 106 cholangiocarcinomas, EBP50 was delocalized to the cytoplasm of tumor cells in 66% of the cases. Ectopic expression of EBP50 was correlated with the presence of satellite nodules and with the expression of EGFR, which was at the plasma membrane, implying a loss of interaction with EBP50 in these cases. In vitro, loss of interaction between EBP50 and EGFR was mimicked by EBP50 depletion using a small interfering RNA approach in human biliary carcinoma cells co-expressing the two proteins at their plasma membrane, and in which interaction between EBP50 and EGFR was validated. EBP50 depletion caused an increase in EGFR expression at their surface, and a sustained activation of the receptor and of its downstream effectors (extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3) in both basal and EGF-stimulated conditions. Cells lacking EBP50 showed epithelial-to-mesenchymal transition-associated features, including reduction in E-cadherin and cytokeratin-19 expression, induction of S100A4 and of the E-cadherin transcriptional repressor, Slug, and loss of cell polarity. Accordingly, depletion of EBP50 induced the disruption of adherens junctional complexes, the development of lamellipodia structures and the subsequent acquisition of motility properties. All these phenotypic changes were prevented upon inhibition of EGFR tyrosine kinase by gefitinib. These findings indicate that loss of EBP50 at the plasma membrane in tumor cells may contribute to biliary carcinogenesis through EGFR activation.

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

Cited by 35 publications

References 24 publications

Necl2 regulates epidermal adhesion and wound repair

Necl2 regulates epidermal adhesion and wound repair

Decreased expression of CADM1 and CADM4 are associated with advanced stage breast cancer

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

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