Recruitment of vimentin to the cell surface by β3 integrin and plectin mediates adhesion strength

Bhattacharya, Ramona; Gonzalez, Annette M.; DeBiase, Phillip J.; Trejo, Humberto E.; Goldman, Robert D.; Flitney, Frederick W.; Jones, Jonathan

doi:10.1242/jcs.043042

Cited by 133 publications

(148 citation statements)

References 47 publications

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“…Inflammation is considered to be a major consequence of SASP, which proposes that senescent fibroblasts are primed to become proinflammatory cells. Despite lacking a secretory signal sequence, vimentin is externalized on the cell surface and secreted in various physiological conditions that involve induction of proinflammatory signals, suggesting a possible phenotypic connection to SASP (42,43,50,51). We therefore sought to measure secreted vimentin using our polyreactive 9H4 antibody as a potential readout of senescent cells in vitro and in vivo.…”

Section: H4 Recognizes Vimentin and Oxidative Posttranslational Modimentioning

confidence: 99%

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Frescas

Roux

Aygun‐Sunar

et al. 2017

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

113

103

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Studying the phenomenon of cellular senescence has been hindered by the lack of senescence-specific markers. As such, detection of proteins informally associated with senescence accompanies the use of senescence-associated β-galactosidase as a collection of semiselective markers to monitor the presence of senescent cells. To identify novel biomarkers of senescence, we immunized BALB/c mice with senescent mouse lung fibroblasts and screened for antibodies that recognized senescence-associated cell-surface antigens by FACS analysis and a newly developed cell-based ELISA. The majority of antibodies that we isolated, cloned, and sequenced belonged to the IgM isotype of the innate immune system. In-depth characterization of one of these monoclonal, polyreactive natural antibodies, the IgM clone 9H4, revealed its ability to recognize the intermediate filament vimentin. By using 9H4, we observed that senescent primary human fibroblasts express vimentin on their cell surface, and MS analysis revealed a posttranslational modification on cysteine 328 (C328) by the oxidative adduct malondialdehyde (MDA). Moreover, elevated levels of secreted MDA-modified vimentin were detected in the plasma of aged senescence-accelerated mouse prone 8 mice, which are known to have deregulated reactive oxygen species metabolism and accelerated aging. Based on these findings, we hypothesize that humoral innate immunity may recognize senescent cells by the presence of membrane-bound MDA-vimentin, presumably as part of a senescence eradication mechanism that may become impaired with age and result in senescent cell accumulation.aging | oxidative posttranslational modifications | biomarker | SAMP8 | malondialdehyde

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Section: H4 Recognizes Vimentin and Oxidative Posttranslational Modimentioning

confidence: 99%

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Frescas

Roux

Aygun‐Sunar

et al. 2017

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

113

103

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“…Several studies have suggested that the intermediate filament protein vimentin is associated with focal adhesions and with the regulation of focal adhesion size and stabilisation of ECM-cell adhesion sites (Bhattacharya et al, 2009;Tsuruta and Jones, 2003). Because vimentin and nestin are binding partners, we wanted to study whether nestin was also associated with focal adhesions and what the implications of this are.…”

Section: Nestin Regulates the Localisation Of Pfakmentioning

confidence: 99%

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Hyder

Lazaro

Pylvänäinen

et al. 2014

Journal of Cell Science

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BSTRACTNestin, an intermediate filament protein and marker of undifferentiated cells, is expressed in several cancers. Nestin is important for neuronal survival and is a regulator of myogenesis but its function in malignancy is ambiguous. We show that nestin downregulation leads to a redistribution of phosphorylated focal adhesion kinase (pFAK, also known as PTK2) to focal adhesions and alterations in focal adhesion turnover. Nestin downregulation also leads to an increase in the protein levels of integrin a5b1 at the cell membrane, activation of integrin b1 and an increase in integrin clustering. These effects have striking consequences for cell invasion, as nestin downregulation leads to a significant increase in pFAK-and integrin-dependent matrix degradation and cell invasion. Our results indicate that nestin regulates the localisation and functions of FAK and integrin. Because nestin has been shown to be prevalent in a number of specific cancers, our observations have broad ramifications for the roles of nestin in malignant transformation.

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“…Moreover, through integrin-linked kinase, integrin can regulate expression and function of vimentin. The levels of vimentin and integrin play a key role in tissue homeostasis as well, and their hyperexpression leads to tumorigenesis [25,26] . We detected and observed that the mRNA expression levels of α v -integrin and vimentin could be mediated by heparin treatment.…”

Section: Effect Of Heparin On Brdu Incorporation and Ki67 Expression mentioning

confidence: 99%

Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis

et al. 2012

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Aim: To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin. Methods: Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 μg/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10-luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-β, E-cadherin, and α v -integrin was measured by RT-PCR. Results: Heparin 25 and 125 μg/mL significantly inhibited the proliferation, arrested the cells in G 1 phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down-regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 μg/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of α v -integrin. Heparin 125 μg/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-β mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells. Conclusion: Heparin inhibited PC-3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and α v -integrin expression.

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Recruitment of vimentin to the cell surface by β3 integrin and plectin mediates adhesion strength

Cited by 133 publications

References 47 publications

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody

Nestin regulates prostate cancer cell invasion by influencing FAK and integrin localisation and functions

Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis

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