Molecular Playground/IntegrinBeta1: Difference between revisions
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==Studying Integrin Beta-1'' in vitro''== | ==Studying Integrin Beta-1'' in vitro''== | ||
Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins), and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here</scene>. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. | Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function ''in vitro''. Common approaches use simple end point gene or protein expression analysis, however, ''in vitro'' studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins), and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM. When beta1 dimerizes with alpha1, it can bind to both collagens and laminins, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown <scene name='60/609777/With_antibody/4'>here</scene>. Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red. | ||
==Peyton Lab Research Interests== | ==Peyton Lab Research Interests== | ||
Revision as of 02:55, 20 November 2014
One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground. Molecular Playground banner: "
Banner: Studying integrin-mediated metastasis in vitro
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StructureStructure
Blue-Alpha 5 chain Red-Beta 1 chain Grey-SG/19 Fab fragment light chain Green-SG/19 Fab fragment heavy chain
FunctionFunction
Integrins are a class of surface proteins that bind to extracellular matrix components and transmit chemical and mechanical cues to internal signaling pathways. Integrin beta 1 binds many proteins when dimerized with an alpha subunit, including collagen, laminin and fibronectin. Integrin adhesion to the extra cellular matrix is key for cell ability to adhere, migrate and proliferate in both 2D and 3D systems. These will eventually form adhesion complexes, which regulate actomyocin polymerization. During migration, cells continually form new focal adhesions at the leading edge of the cell and release adhesion complexes at the back of the cell, enabling forward movement.
Here are the N-acetyl-D-glucosamine may regulate integrin signaling during cancer cell migration.[1]
Integrins and cancerIntegrins and cancer
Integrins binding to the extracellular matrix provide cells the ability to migrate and remodel the surrounding microenvironment. Integrins are extremely important in cancer metastasis and the progression of solid tumors. Cells bind to extracellular matrix proteins, like, with integrins to stimulate survival, migration/invasion, and proliferation [2]. Though high expression of integrin beta 1 has been shown to drive primary tumor progression and metastasis, targeting integrins for cancer treatment has seen limited clinical efficacy [3]. These failures stem from differential integrin expression between cancer cells, but new technologies to screen cancer cell populations are being developed to affective therapies on a patient-specific level [4]. These technologies will likely allow for more selective treatment and better clinical efficacy for integrin inhibitors.
Studying Integrin Beta-1 in vitroStudying Integrin Beta-1 in vitro
Due to their roles in both disease and cell-matrix interactions, there is a growing interest in studying integrin function in vitro. Common approaches use simple end point gene or protein expression analysis, however, in vitro studies allow for functional analysis to observe intern binding interactions in single living cells. Tools include siRNA to prevent integrin gene expression, integrin binding peptides (i.e., the RGD peptide) which bind to integrins competitively with ECM proteins), and function-affecting antibodies which can bind to integrin heterodimers and prevent binding to the ECM. When beta1 dimerizes with alpha1, it can bind to both collagens and laminins, which are both large components of the ECM of many tissues. Integrin alpha1 beta1 binding to a function affecting integrin antibody is shown . Chains A and B of the I domain are blue, and the heavy and light chains of the Fab fragment are red.
Peyton Lab Research InterestsPeyton Lab Research Interests
The Peyton lab studies how cells process chemical and physical cues from the extracellular matrix and how these interactions play a role in the progression of cardiovascular disease and cancer. We aim to understand the downstream signaling pathways activated when cells use their integrins to bind to matrix and how this translates to the disease of interest. We are further interested in how integrins can be biomarkers in disease, because they transduce signals from the diseased microenvironment to cells, likely facilitating disease progression in some cases. </StructureSection>
ReferencesReferences
[1] C. Saravanan, F. Liu, I.K. Gipson and N. Panjwani1. Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on 31 integrin. Journal of Cell Science 122, 3684-3693 Published by The Company of Biologists (2009). doi:10.1242/jcs.045674.
[2] Desgrossellier JS, and Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nature Reviews Cancer 10, 9-22 (January 2010) | doi:10.1038/nrc2748
[3]Dos Santos PB, Zanetti JS, Ribeiro-Silva A, Beltrão EIC. Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study. Diagn Pathol 7:104.(2012)
[4] Barney LE, Dandley EC, Jansen LE, Reich NG, Mercurio AM, Peyton SR. “A Cell-ECM Screening Method to Predict Breast Cancer Metastasis”. (2014) In Review.