Tight junction-based epithelial microenvironment and cell proliferation

Tsukita, Sachiko; Yamazaki, Y.; Katsuno, Tatsuya; Tamura, Atsushi

doi:10.1038/onc.2008.344

Cited by 327 publications

(302 citation statements)

References 84 publications

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“…A main task of the EPP is the creation of TJs at the apical-lateral border. TJs are epithelialspecific structures composed of trasmembrane proteins, for example, occludin and the claudin family, that interact homotypically with molecules in the neighboring cell and with peripheral proteins (ZO1, ZO3, cingulin) in the cytoplasmic side (see Tsukita et al, 2008 andCereijido et al, 2008). TJs have the ability to act as a fence between proteins in the apical and lateral domains.…”

Section: Domain-identity Machinerymentioning

confidence: 99%

The epithelial polarity program: machineries involved and their hijacking by cancer

2008

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The Epithelial Polarity Program (EPP) adapts and integrates three ancient cellular machineries to construct an epithelial cell. The polarized trafficking machinery adapts the cytoskeleton and ancestral secretory and endocytic machineries to the task of sorting and delivering different plasma membrane (PM) proteins to apical and basolateral surface domains. The domain-identity machinery builds a tight junctional fence (TJ) between apical and basolateral PM domains and adapts ancient polarity proteins and polarity lipids on the cytoplasmic side of the PM, which have evolved to perform a diversity of polarity tasks across cells and species, to provide 'identity' to each epithelial PM domain. The 3D organization machinery utilizes adhesion molecules as positional sensors of other epithelial cells and the basement membrane and small GTPases as integrators of positional information with the activities of the domain-identity and polarized trafficking machineries. Cancer is a disease mainly of epithelial cells (90% of human cancers are carcinomas that derive from epithelial cells) that hijacks the EPP machineries, resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. Here, we review how the EPP integrates its three machineries and the strategies used by cancer to hijack them.

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Section: Domain-identity Machinerymentioning

confidence: 99%

The epithelial polarity program: machineries involved and their hijacking by cancer

2008

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“…Because of this ability, tight junction proteins are believed to be involved in the regulation of proliferation, differentiation, and other cellular functions. Claudin-1 is the 5 main component of the tight junction family of proteins and its expression is often celltype-and tissue-dependent 24,25 . Expression of claudin-1 is negatively regulated by 2 related transcription factors, Snail and Slug, which are involved in the induction of epithelial-mesenchymal transition (EMT), which is a normal developmental process characterized by loss of cell adhesion and increased mobility; EMT is now considered to contribute to invasive and metastatic tumor growth 26 .…”

Section: Introductionmentioning

confidence: 99%

Claudin-1 Has Tumor Suppressive Activity and Is a Direct Target of RUNX3 in Gastric Epithelial Cells

Chang

Ito

et al. 2010

Gastroenterology

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“…Seventy‐six genes showed a genetic aberration incidence of 10% or more in CIMP‐positive RCCs ( n = 19), whereas only four genes did so in CIMP‐negative RCCs ( n = 87) (Tables 2 and 3). Genes encoding microtubule‐associated proteins, such as DNAH2, DNAH5, DNAH10 ,31 RP1 32 and HAUS8 ,33, 34 those involved in histone modification, such as NCOA1 ,35 those involved in cell adhesion, such as CELSR1, CELSR2 ,36 CTNND1 ,37 LAMC2 38 and TJP1 ,39 and tumor‐related genes such as BAP1 40 and ATM ,41 were frequently mutated in CIMP‐positive RCCs (Table 3). As shown in Tables 2 and 3, 235 genetic aberrations (173 non‐synonymous single‐nucleotide mutations and 62 indels) revealed by whole‐exome analysis in the initial cohort were all successfully verified by Sanger sequencing.…”

Section: Resultsmentioning

confidence: 99%

“…Whether or not aberrations of genes involved in histone modification, such as NCOA1 ,35 participate in the acquisition of epigenetic characteristics in CIMP‐positive RCCs warrants further examination. Aberrations of genes involved in cell adhesion, such as CELSR1, CELSR2 ,36 CTNND1 ,37 LAMC2 38 and TJP1 ,39 may affect the invasiveness and metastatic potential of CIMP‐positive RCCs (CIMP‐positive RCCs show invasive growth and distant metastasis more frequently than CIMP‐negative RCCs13). Moreover, genetic aberrations of microtubule‐associated proteins, such as DNAH2, DNAH5, DNAH10 ,31 RP1 32 and HAUS8 ,33, 34 may be correlated with dysregulation of the spindle checkpoint in CIMP‐positive RCCs.…”

Section: Discussionmentioning

confidence: 99%

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas

Arai¹,

Gotoh²,

Tian³

et al. 2015

Intl Journal of Cancer

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CpG‐island methylator phenotype (CIMP)‐positive clear cell renal cell carcinomas (RCCs) are characterized by accumulation of DNA hypermethylation of CpG islands, clinicopathological aggressiveness and poor patient outcome. The aim of this study was to clarify the molecular pathways participating in CIMP‐positive renal carcinogenesis. Genome (whole‐exome and copy number), transcriptome and proteome (two‐dimensional image converted analysis of liquid chromatography‐mass spectrometry) analyses were performed using tissue specimens of 87 CIMP‐negative and 14 CIMP‐positive clear cell RCCs and corresponding specimens of non‐cancerous renal cortex. Genes encoding microtubule‐associated proteins, such as DNAH2, DNAH5, DNAH10, RP1 and HAUS8, showed a 10% or higher incidence of genetic aberrations (non‐synonymous single‐nucleotide mutations and insertions/deletions) in CIMP‐positive RCCs, whereas CIMP‐negative RCCs lacked distinct genetic characteristics. MetaCore pathway analysis of CIMP‐positive RCCs revealed that alterations of mRNA or protein expression were significantly accumulated in six pathways, all participating in the spindle checkpoint, including the “The metaphase checkpoint (p = 1.427 × 10−6),” “Role of Anaphase Promoting Complex in cell cycle regulation (p = 7.444 × 10−6)” and “Spindle assembly and chromosome separation (p = 9.260 × 10−6)” pathways. Quantitative RT‐PCR analysis revealed that mRNA expression levels for genes included in such pathways, i.e., AURKA, AURKB, BIRC5, BUB1, CDC20, NEK2 and SPC25, were significantly higher in CIMP‐positive than in CIMP‐negative RCCs. All CIMP‐positive RCCs showed overexpression of Aurora kinases, AURKA and AURKB, and this overexpression was mainly attributable to increased copy number. These data suggest that abnormalities of the spindle checkpoint pathway participate in CIMP‐positive renal carcinogenesis, and that AURKA and AURKB may be potential therapeutic targets in more aggressive CIMP‐positive RCCs.

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Tight junction-based epithelial microenvironment and cell proliferation

Cited by 327 publications

References 84 publications

The epithelial polarity program: machineries involved and their hijacking by cancer

The epithelial polarity program: machineries involved and their hijacking by cancer

Claudin-1 Has Tumor Suppressive Activity and Is a Direct Target of RUNX3 in Gastric Epithelial Cells

Alterations of the spindle checkpoint pathway in clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas

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