Tight junctions in cancer metastasis

Martin, Tracey Amanda; Mason, Malcolm David; Jiang, Wen Guo

doi:10.2741/3726

Cited by 94 publications

(69 citation statements)

References 180 publications

(142 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). Furthermore, given the prognostic value of claudin 4 total protein expression in various tumor types (Ersoz et al, 2011;Sung et al, 2011;Szasz et al, 2011) and the association between loss of TJs and metastatic behavior (Martin et al, 2011), our results also provide additional evidence that IQGAP1 might be a potential therapeutic target for the treatment of advanced cancers.…”

Section: Discussionmentioning

confidence: 55%

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

Tanos

Bay

Salvarezza

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

IQGAP1 is a scaffolding protein previously implicated in adherens junction formation. However, its role in the establishment or maintenance of tight junctions (TJs) has not been explored. We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins, and we systematically tested this hypothesis in the model Madin-Darby canine kidney (MDCK) cell line. We find that IQGAP1 silencing enhances a transient increase in transepithelial electrical resistance (TER) observed during the early stages of TJ formation (Cereijido et al., 1978). Quantitative microscopy and biochemical experiments suggest that this effect of IQGAP1 on TJ assembly is accounted for by reduced expression and TJ recruitment of claudin 2, and increased TJ recruitment of claudin 4. Furthermore, we show that IQGAP1 also regulates TJ formation through its interactor CDC42, because IQGAP1 knockdown increases the activity of the CDC42 effector JNK and dominantnegative CDC42 prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide evidence that IQGAP1 modulates TJ formation by a twofold mechanism: (1) controlling the expression and recruitment of claudin 2 and recruitment of claudin 4 to the TJ, and (2) transient inhibition of the CDC42-JNK pathway.

show abstract

Section: Discussionmentioning

confidence: 55%

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

Tanos

Bay

Salvarezza

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In breast cancer cells, NRP/B was able to enhance oxidative stress responses via the Nrf2 pathway (35). More than 13 cell adhesion proteins in the present study may play roles in the intercellular and cell-extracellular matrix interactions of cancer, leading to cancer invasion or metastasis (36), or participating in signal transduction, cell growth and differentiation (37). E-cadherin is one prominent adhesion molecule that forms the E-cadherin-catenin complex which plays a role in epithelial cell-cell adhesion and differentiation (38), in particular serving as a potent invasion/tumor suppressor of breast cancer (39).…”

Section: Discussionmentioning

confidence: 61%

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

Liu¹,

Jin²,

Shen³

2012

Oncology Letters

View full text Add to dashboard Cite

Abstract. The aim of this study was to better understand the altered functional modules in breast cancer at pathway and network levels. An integrated bioinformatics analysis of differentially expressed proteins in human breast cancer was performed. Breast cancer protein profiles were constructed by data mining proteins in literature and public databases, including 1031 proteins with 153 secretory and 69 cell surface proteins. An experimental investigation was performed by two-dimensional electrophoresis, and 4 proteins were further validated by western blotting. Enriched bioinformatics functions were clustered. This study may be used as a reference in further studies to help identify the underlying biological interactions associated with breast cancer and discover potential cancer targets. IntroductionBreast cancer is the most common neoplasia in women and its pathogenesis is related to an acquired or inherited genetic disorder influenced by environmental, behavioral or reproductive factors (1). Cancer biomarker discovery is important for both cancer biology and clinical applications. These markers may come from DNA, RNA, miRNA or proteins (2), with proteins being the most significant (3).The development and improvement of biotechnologies has allowed researchers to perform high-throughput analyses of genomes, transcriptomes and proteomes in health and disease, and identify hundreds of potential biomarkers (4), offering the potential to discover diagnostic, prognostic or therapeutic targets. However, less than two dozen cancer biomarkers are currently approved by the Food and Drug Administration (FDA) (5), including only 9 protein biomarkers identified in the blood (6). Due to the lack of sensitivity and specificity of these known biomarkers (7), researchers continue to search for more significant targets. Proteomics is a promising approach for the discovery of cancer targets and biomarkers (8). The mapping of proteome profiles and differential proteomics has been widely performed in breast cancer to identify potential biomarkers (9). The identified proteins were reported to have potential clinical significance, and certain proteins may be used as potential diagnostic, prognostic or predictive biomarkers (10,11,12,13,14). However, due to the heterogeneity in the different studies, including experimental design, sample collection and classification and analytical method (15), these results lack good reproducibility and require further validation before they can be used in clinical detection and to explain the underlying mechanisms of breast cancer. In addition, few protein candidates were warranted to be specific to breast cancer, and were often differentially expressed in other cancer types (16). Hence, research encountered the challenge of how to decipher and use these individual results and bring them into clinical applications. In addition, an understanding of the underlying biological mechanisms of carcinogenesis and the altered molecular events in breast cancer at integrated pathway levels is necessary. Prot...

show abstract

“…However, several functions were commonly clustered in the cancers, including cell cycle, mitochondrion, cytoskeleton, cell adhesion, protein localization, and tight junction. These functions have previously been shown to be involved in cancer progression (Wallace, 2012;Williams and Stoeber, 2012), invasion (Behrens, 1993), and metastasis (Martin et al, 2011).…”

Section: Discussionmentioning

confidence: 95%

Novel bioinformatic identification of differentially expressed tissue-specific and cancer-related proteins from the Human Protein Atlas for biomarker discovery

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Identification of cancer-associated and tissue-specific proteins is important for research on carcinogenesis mechanisms and biomarker discovery. Here we performed a new strategy to identify candidate cancer proteins by mining immunohistochemistry protein profiles. Proteins with quantitative values from 14 normal tissues and their corresponding cancer tissues were compared and analyzed using bioinformatics. The final results included identification of tissue-specific proteins and differentially expressed proteins in different cancer types that are primarily involved in energy metabolism and cell invasion. From the tissue-specific proteins, secreted and membrane proteins were further screened and functionally clustered. These primarily belonged to the gene families of endogenous ligands, cluster of differentiation molecules, and solute carriers, and were mainly involved in the processes of cell motility, hormone metabolism, adhesion, and transport. Further studies are warranted to validate the candidates identified herein and substantiate the suggested enriched functions. The results 4557-4565 (2015) from this study might provide a reliable resource to study underlying carcinogenesis mechanisms and discover potential cancer targets for the development of therapeutic targets and of early diagnosis and disease response markers.

show abstract

Tight junctions in cancer metastasis

Cited by 94 publications

References 180 publications

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

Novel bioinformatic identification of differentially expressed tissue-specific and cancer-related proteins from the Human Protein Atlas for biomarker discovery

Contact Info

Product

Resources

About