Tensegrin in context

Zargham, Ramin

doi:10.4161/cam.4.4.12403

Cited by 8 publications

(4 citation statements)

References 62 publications

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“…3). The α8 subunit is believed to exclusively heterodimerize with the β1 integrin subunit 26,27 , hence the staining represents α8β1. The control cells, 66cl4-EV, showed no expression of NPNT, and focal distribution of α8β1 (Fig.…”

Section: Npnt Transcript Is Up-regulated In Human Bc and Linked To Pomentioning

confidence: 99%

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains

Magnussen

Toraskar

Wilhelm

et al. 2020

Sci Rep

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this study demonstrates a role for the extracellular matrix protein nephronectin (npnt) in promoting experimental breast cancer brain metastasis, possibly through enhanced binding to-and migration through brain endothelial cells. With the introduction of more targeted breast cancer treatments, a prolonged survival has resulted during the last decade. Consequently, an increased number of patients develop metastasis in the brain, a challenging organ to treat. We recently reported that NPNT was highly expressed in primary breast cancer and associated with unfavourable prognosis. The current study addresses our hypothesis that npnt promotes brain metastases through its integrin-binding motifs. SAGE-sequencing revealed that NPNT was significantly up-regulated in human breast cancer tissue compared to pair-matched normal breast tissue. Human brain metastatic breast cancers expressed both NPNT and its receptor, integrin α8β1. Using an open access repository; BreastMark, we found a correlation between high NPNT mRNA levels and poor prognosis for patients with the luminal B subtype. The 66cl4 mouse cell line was used for expression of wild-type and mutant NPNT, which is unable to bind α8β1. Using an in vivo model of brain metastatic colonization, 66cl4-NPNT cells showed an increased ability to form metastatic lesions compared to cells with mutant NPNT, possibly through reduced endothelial adhesion and transmigration. Abbreviations AMPK AMP-activated protein kinase BC Breast cancer EGF Epidermal growth factor EGFR Epidermal growth factor receptor EIE Glutamic acid-isoleucine-glutamic acid ER Estrogen receptor EV Empty vector FFPE Formalin fixed paraffin embedded HER2 Human epidermal growth factor receptor 2 IHC Immunohistochemistry MBEC Mouse brain endothelial cells NPNT Nephronectin

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Section: Npnt Transcript Is Up-regulated In Human Bc and Linked To Pomentioning

confidence: 99%

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains

Magnussen

Toraskar

Wilhelm

et al. 2020

Sci Rep

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“…Integrins are transmembrane αβ heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM molecules. Specifically, α8β1 or tensegrin can bind to several ECM molecules and has been shown to be associated with focal adhesion points, where it participates in the regulation of spreading, adhesion, growth, and survival in different neuronal and mesenchymal-derived cell types ( 30 , 31 ).…”

Section: Role Of Ecm In Biotensegritymentioning

confidence: 99%

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

et al. 2014

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Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is implicated in cell proliferation, differentiation, and apoptosis. Despite present advances, only the tip of the iceberg has so far been uncovered regarding the role of ECM compounds in influencing biotensegrity in pathological processes. Groups of cells, together with the surrounding ground substance, are subject to different and specific forces that certainly influence biological processes. In this paper, we review the current knowledge on the role of ECM elements in determining biotensegrity in malignant processes and describe their implication in therapeutic response, resistance to chemo- and radiotherapy, and subsequent tumor progression. Original data based on the study of neuroblastic tumors will be provided.

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“…This phenotype resembled that of mice with non-functional integrin α8β1 [ 31 ], which triggered Reichardt and colleagues to test whether NPNT was the binding partner of integrin α8β1 [ 11 , 32 ]. Integrin α8β1 is a member of the RGD-binding group of integrins, where the α8 subunit associates exclusively with the β1 subunit [ 44 , 45 ]. The α8 subunit is expressed in vascular and visceral smooth muscle, liver stellate cells, and smooth muscle-like contractile cells.…”

Section: Expression and Functional Roles Of Npntmentioning

confidence: 99%

“…The α8 subunit is expressed in vascular and visceral smooth muscle, liver stellate cells, and smooth muscle-like contractile cells. In addition, the kidney mesenchyme (mesangial cells) expresses α8, as well as one cell type in the alveolar wall of the lungs, most likely the alveolar myofibroblasts [ 44 , 45 , 46 ]. Müller et al reported expression of the α8 subunit in mesenchymal but not epithelial cells of developing organs such as the gut, lung, gonads and the nephrogenic cord [ 31 ].…”

Section: Expression and Functional Roles Of Npntmentioning

confidence: 99%

Nephronectin as a Matrix Effector in Cancer

Magnussen

Toraskar

Hadler‐Olsen

et al. 2021

Cancers

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The extracellular matrix protein nephronectin plays an important regulatory role during embryonic development, controlling renal organogenesis through integrin α8β1 association. Nephronectin has three main domains: five N-terminal epidermal growth factor-like domains, a linker region harbouring two integrin-binding motifs (RGD and LFEIFEIER), and a C-terminal MAM domain. In this review, we look into the domain-related functions of nephronectin, and tissue distribution and expression. During the last two decades it has become evident that nephronectin also plays a role during cancer progression and in particular metastasis. Nephronectin is overexpressed in both human and mouse breast cancer compared to normal breast tissue where the protein is absent. Cancer cells expressing elevated levels of nephronectin acquire increased ability to colonise distant organs. In particular, the enhancer-motif (LFEIFEIER) which is specific to the integrin α8β1 association induces viability via p38 MAPK and plays a role in colonization. Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.

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Tensegrin in context

Cited by 8 publications

References 62 publications

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains

Biotensegrity of the Extracellular Matrix: Physiology, Dynamic Mechanical Balance, and Implications in Oncology and Mechanotherapy

Nephronectin as a Matrix Effector in Cancer

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