p53 regulation of podosome formation and cellular invasion in vascular smooth muscle cells

Mak, Alan S.

doi:10.4161/cam.5.2.14375

Cited by 15 publications

(17 citation statements)

References 85 publications

(95 reference statements)

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“…In culture, aortic VSMC from ApoE -/- /p53 -/- mice produce significantly more podosomes and are more invasive (Fig 5B and 5C), consistent with previous reports from us [3,5,6,10,11]. In those previous studies, we have identified p53 as a suppressor of Src-induced podosome formation and proposed that p53 acts by upregulating the expression of two anti-invasion regulators: caldesmon, an actin-binding protein and a negative regulator of podosome assembly [10], and PTEN that inhibits the Src-mediated PI3K-Akt and Stat3 pro-invasion pathways [11,32].…”

Section: Discussionsupporting

confidence: 92%

“…While increased VSMC migration in p53-null VSMC may contribute to initiation of atherosclerotic plaque formation and stabilization of the fibrous cap, invasion of the extracellular matrix is required for media-to-intima migration [3,7]. As shown in Fig 3A and 3B, holes in the elastic fiber layers were observed during early lesion formation in the aortas of mice that may indicate digestion of ECM by VSMC.…”

Section: Resultsmentioning

confidence: 99%

“…Media-to-intima migration of VSMC in the arterial wall is a hallmark characteristic of atherosclerosis and plaque formation. This is achieved by remodelling of the actin cytoskeleton to produce actin-based membrane protrusions such as ruffles and podosomes [3–7]. Release of proteases by podosomes, primarily matrix metalloproteases (MMPs), enables digestion of extracellular matrix (ECM) proteins, hence clearing a path for migration [8].…”

Section: Introductionmentioning

confidence: 99%

“…We have shown in vitro that p53 also acts as a suppressor of cell migration and invasion in VSMC by down regulating the formation of circular dorsal ruffles (CDR) and podosomes [3,5,6,10,11]. A number of studies have been attempted to explore the anti-proliferative and pro-apoptotic roles of p53 in atherosclerosis using genetically engineered mouse models [12–20].…”

Section: Introductionmentioning

confidence: 99%

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Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in mice

et al. 2017

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In vitro and in vivo evidence has indicated that the tumor suppressor, p53, may play a significant role in the regulation of atherosclerotic plaque formation. In vivo studies using global knockout mice models, however, have generated inconclusive results that do not address the roles of p53 in various cell types involved in atherosclerosis. In this study, we have specifically ablated p53 in vascular smooth muscle cells (VSMC) in the ApoE-/- mouse model to investigate the roles of p53 in VSMC in atherosclerotic plaque formation and stability. We found that p53 deficiency in VSMC alone did not affect the overall size of atherosclerotic lesions. However, there was a significant increase in the number of p53-/- VSMC in the fibrous caps of atherosclerotic plaques in the early stages of plaque development. Loss of p53 results in migration of VSMC at a faster rate using wound healing assays and augments PDGF-induced formation of circular dorsal ruffles (CDR), known to be involved in cell migration and internalization of surface receptors. Furthermore, aortic VSMC from ApoE-/- /p53-/- mice produce significantly more podosomes and are more invasive. We conclude that p53-/- VSMC are enriched in the fibrous caps of lesions at early stages of plaque formation, which is caused in part by an increase in VSMC migration and invasion as shown by p53-/- VSMC in culture having significantly higher rates of migration and producing more CDRs and invasive podosomes.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in mice

et al. 2017

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“…Interestingly, wild-type p53 negatively regulates cell migration and invasion in vascular smooth muscle cells (15), and mutant p53 drives invasion of lung cancer cells by promoting integrin recycling (16). Taken together, these reports suggest cross-regulation of p53 and adhesion-based signaling pathways (17).…”

mentioning

confidence: 84%

Supervillin-mediated Suppression of p53 Protein Enhances Cell Survival

Fang

Luna

2013

Journal of Biological Chemistry

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Background: Supervillin is a membrane-associated actin-and myosin II-regulatory protein that promotes cell growth, adhesion, and invasion. Results: Supervillin inversely regulates p53 levels, binds the p53-stabilizing protein USP7, and regulates the USP7-p53 interaction. Conclusion: Supervillin regulation of p53 through USP7 contributes to cell survival. Significance: This study describes a new locus for cross-talk between cytoskeletal proteins and p53-regulated survival signaling.

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Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts

Uehara

Udagawa

Kobayashi

2018

Cell. Mol. Life Sci.

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Osteoclasts are multinucleated cells responsible for bone resorption. Osteoclasts adhere to the bone surface through integrins and polarize to form actin rings, which are formed by the assembly of podosomes. The area contained within actin rings (also called sealing zones) has an acidic pH, which causes dissolution of bone minerals including hydroxyapatite and the degradation of matrix proteins including type I collagen by the protease cathepsin K. Osteoclasts resorb bone matrices while moving on bone surfaces. Osteoclasts change their cell shapes and exhibit three modes for bone resorption: motile resorbing mode for digging trenches, static resorbing mode for digging pits, and motile non-resorbing mode. Therefore, the actin cytoskeleton is actively remodeled in osteoclasts. Recent studies have revealed that many molecules, such as Rac, Cdc42, Rho, and small GTPase regulators and effectors, are involved in actin cytoskeletal remodeling during the formation of actin rings and resorption cavities on bone slices. In this review, we introduce how these molecules and non-canonical Wnt signaling regulate the bone-resorbing activity of osteoclasts.

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p53 regulation of podosome formation and cellular invasion in vascular smooth muscle cells

Cited by 15 publications

References 85 publications

Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in mice

Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in mice

Supervillin-mediated Suppression of p53 Protein Enhances Cell Survival

Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts

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