Integrins and cadherins join forces to form adhesive networks

Weber, Gregory F.; Bjerke, Maureen A.; DeSimone, Douglas W.

doi:10.1242/jcs.091074

Cited by 34 publications

(36 citation statements)

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“…5E). Numerous observations suggest that cell-cell or cell-matrix adhesion through adhesion molecules, such as integrins and cadherins, regulates cell survival, tumor invasion, and metastasis (24,25). Interestingly, the ability of p53 to regulate cell survival in response to DNA damage is also regulated by cellcell interaction via adhesion molecules (26).…”

Section: Lack Of Ninj1 Up-regulates P53 Expression Potentially Throughmentioning

confidence: 99%

Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality

Cho

Rossi

Jung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The tumor suppressor protein p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest, apoptosis, and senescence. The nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a homophilic adhesion molecule and involved in nerve regeneration. Interestingly, Ninj1 is found to be overexpressed in human cancer, but its role in tumorigenesis is not clear. Here, we found that Ninj1 is transcriptionally regulated by p53 and can be induced by DNA damage in a p53-dependent manner. We also found that knockout or knockdown of Ninj1 increases p53 expression potentially through enhanced p53 mRNA translation. In addition, we found that Ninj1 deficiency suppresses cell proliferation but enhances apoptosis and premature senescence in a p53-dependent manner. Consistent with this, we found that mice heterozygous in ninj1 are hypersensitive to ionizing radiation-induced lethality, along with increased expression of p53 in thymus. Taken together, we provided evidence that Ninj1 is a p53 target and modulates p53 mRNA translation and p53-dependent premature senescence, cell proliferation, apoptosis, and radiationinduced mortality in vitro and in vivo. Thus, we postulate that as a membrane adhesion molecule, Ninj1 is an ideal target to regulate p53 activity via the p53-Ninj1 loop. cellular senescence | radiosensitivity

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Section: Lack Of Ninj1 Up-regulates P53 Expression Potentially Throughmentioning

confidence: 99%

Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality

Cho

Rossi

Jung

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…It is accompanied by a profoundly altered mesenchymal gene expression program, which is characterized by loss of epithelial keratins like Ecadherin and induction of mesenchymal vimentin (41). EMT could be categorized into three subtypes based upon respective biologic effects (5).…”

Section: Anxa2 Knockdown Compromises Growth Metastasis and Proangiomentioning

confidence: 99%

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Zhou

et al. 2012

Molecular & Cellular Proteomics

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Adenomyosis is a common estrogen-dependent disorder of females characterized by a downward extension of the endometrium into the uterine myometrium and neovascularization in ectopic lesions. It accounts for chronic pelvic pain, dysmenorrhea, menorrhagia, and infertility in 8.8 -61.5% women worldwide. However, the molecular mechanisms for adenomyosis development remain poorly elucidated. Here, we utilized a two-dimensional polyacrylamide gel electrophoresis/MS-based proteomics analysis to compare and identify differentially expressed proteins in matched ectopic and eutopic endometrium of adenomyosis patients. A total of 93 significantly altered proteins were identified by tandem MS analysis. Further cluster analysis revealed a group of estrogen-responsive proteins as dysregulated in adenomyosis, among which annexin A2, a member of annexin family proteins, was found up-regulated most significantly in the ectopic endometrium of adenomyosis compared with its eutopic counterpart. Overexpression of ANXA2 was validated in ectopic lesions of human adenomyosis and was found to be tightly correlated with markers of epithelial to mesenchymal transition and dysmenorrhea severity of adenomyosis patients. Functional analysis demonstrated that estrogen could remarkably up-regulate ANXA2 and induce epithelial to mesenchymal transition in an in vitro adenomyosis model. Enforced expression of ANXA2 could mediate phenotypic mesenchymal-like cellular changes, with structural and functional alterations in a ␤-catenin/T-cell factor (Tcf) signaling-associated manner, which could be reversed by inhibition of ANXA2 expression. We also proved that enforced expression of ANXA2 enhanced the proangiogenic capacity of adenomyotic endometrial cells through HIF-1␣/VEGF-A pathway. In vivo, we demonstrated that ANXA2 inhibition abrogated endometrial tissue growth, metastasis, and angiogenesis in an adenomyosis nude mice model and significantly alleviated hyperalgesia. Taken together, our data unraveled a dual role for ANXA2 in the pathogenesis of human adenomyosis through conferring endometrial cells both metastatic potential and proangiogenic capacity, which could serve as a potential therapeutic target for the treatment of adenomyosis patients.

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“…Cell-cell and cell-substrate adhesion is mediated by specific interactions between cell surface receptors and ligands (1,2). In turn, the kinetics of ligand binding has major effects on the rate of cell adherence and release under the influence of external mechanical factors and under physiological and pathophysiological conditions (3)(4)(5).…”

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confidence: 99%

Resolving Two-dimensional Kinetics of the Integrin αIIbβ3-Fibrinogen Interactions Using Binding-Unbinding Correlation Spectroscopy

Litvinov

Mekler

Shuman

et al. 2012

Journal of Biological Chemistry

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Background:The two-dimensional kinetics of receptor-ligand interactions determines cell adherence and release. Results: Based on kinetic parameters, time-and force-dependent transitions of bimolecular integrin ␣IIb␤3-fibrinogen complex were revealed. Conclusion: Coupled force-free binding and forced unbinding kinetics reflects dynamics of surface-attached receptor and ligand molecules. Significance: A new approach to explore the mechanism and kinetics of bimolecular interactions has been proposed.

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Integrins and cadherins join forces to form adhesive networks

Cited by 34 publications

References 0 publications

Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality

Ninjurin1, a target of p53, regulates p53 expression and p53-dependent cell survival, senescence, and radiation-induced mortality

Proteomics Identification of Annexin A2 as a Key Mediator in the Metastasis and Proangiogenesis of Endometrial Cells in Human Adenomyosis

Resolving Two-dimensional Kinetics of the Integrin αIIbβ3-Fibrinogen Interactions Using Binding-Unbinding Correlation Spectroscopy

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