scholarly journals Heat Shock Protein 27 Phosphorylation Regulates Tumor Cell Migration under Shear Stress

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 50 ◽  
Author(s):  
Baohong Zhang ◽  
Fei Xie ◽  
Aziz Aziz ◽  
Shuai Shao ◽  
Wang Li ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cell Migration ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cell ◽  
Fluorescent Protein ◽  
Resonance Energy ◽  
Leading Edge ◽  
Heat Shock Protein 27 ◽  
Tumor Cell Migration

Heat shock protein 27 (HSP27) is a multifunctional protein that undergoes significant changes in its expression and phosphorylation in response to shear stress stimuli, suggesting that it may be involved in mechanotransduction. However, the mechanism of HSP27 affecting tumor cell migration under shear stress is still not clear. In this study, HSP27-enhanced cyan fluorescent protein (ECFP) and HSP27-Ypet plasmids are constructed to visualize the self-polymerization of HSP27 in living cells based on fluorescence resonance energy transfer technology. The results show that shear stress induces polar distribution of HSP27 to regulate the dynamic structure at the cell leading edge. Shear stress also promotes HSP27 depolymerization to small molecules and then regulates polar actin accumulation and focal adhesion kinase (FAK) polar activation, which further promotes tumor cell migration. This study suggests that HSP27 plays an important role in the regulation of shear stress-induced HeLa cell migration, and it also provides a theoretical basis for HSP27 as a potential drug target for metastasis.

scholarly journals Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility

2006 ◽  
Vol 176 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Erik Sahai ◽  
Raquel Garcia-Medina ◽  
Jacques Pouysségur ◽  
Emmanuel Vial
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Rho Gtpases ◽  
Rho Kinase ◽  
Cell Movement ◽  
Leading Edge ◽  
Cell Periphery ◽  
Tumor Cell Migration ◽  
Tumor Cell Motility

Rho GTPases participate in various cellular processes, including normal and tumor cell migration. It has been reported that RhoA is targeted for degradation at the leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this is required for the formation of protrusions. We report that Smurf1-dependent RhoA degradation in tumor cells results in the down-regulation of Rho kinase (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell periphery. The localized inhibition of contractile forces is necessary for the formation of lamellipodia and for tumor cell motility in 2D tissue culture assays. In 3D invasion assays, and in in vivo tumor cell migration, the inhibition of Smurf1 induces a mesenchymal–amoeboid–like transition that is associated with a more invasive phenotype. Our results suggest that Smurf1 is a pivotal regulator of tumor cell movement through its regulation of RhoA signaling.

scholarly journals Selective renal overexpression of human heat shock protein 27 reduces renal ischemia-reperfusion injury in mice

2010 ◽  
Vol 299 (2) ◽  
pp. F347-F358 ◽  
Author(s):  
Minjae Kim ◽  
Sang Won Park ◽  
Mihwa Kim ◽  
Sean W. C. Chen ◽  
William T. Gerthoffer ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Heat Shock Protein 27 ◽  
Renal Ischemia ◽  
Specific Expression ◽  
Mrna Induction

We have previously shown that exogenous and endogenous A1 adenosine receptor (A1AR) activation protected against renal ischemia-reperfusion (IR) injury in mice by induction and phosphorylation of heat shock protein 27 (HSP27). With global overexpression of HSP27 in mice, however, there was a paradoxical increase in systemic inflammation with increased renal injury after an ischemic insult due to increased NK1.1 cytotoxicity. In this study, we hypothesized that selective renal expression of HSP27 in mice would improve renal function and reduce injury after IR. Mice were subjected to renal IR injury 2 days after intrarenal injection of saline or a lentiviral construct encoding enhanced green fluorescent protein (EGFP) or human HSP27 coexpressing EGFP (EGFP-huHSP27). Mice with kidney-specific reconstitution of huHSP27 had significantly lower plasma creatinine, renal necrosis, apoptosis, and inflammation as demonstrated by decreased proinflammatory cytokine mRNA induction and neutrophil infiltration. In addition, there was better preservation of the proximal tubule epithelial filamentous (F)-actin cytoskeleton in the huHSP27-reconstituted groups than in the control groups. Furthermore, huHSP27 overexpression led to increased colocalization with F-actin in renal proximal tubules. Taken together, these findings have important clinical implications, as they imply that kidney-specific expression of HSP27 through lentiviral delivery is a viable therapeutic option in attenuating the effects of renal IR.

scholarly journals Cancer-associated mutations in the protrusion-targeting region of p190RhoGAP impact tumor cell migration

2016 ◽  
Vol 214 (7) ◽  
pp. 859-873 ◽  
Author(s):  
Fabien Binamé ◽  
Aurélien Bidaud-Meynard ◽  
Laure Magnan ◽  
Léo Piquet ◽  
Bertille Montibus ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Leading Edge ◽  
Negative Regulator ◽  
Actin Binding ◽  
Tumor Cell Migration ◽  
Spatiotemporal Regulation ◽  
Localization Sequence ◽  
Actin Protrusions ◽  
And Function

Spatiotemporal regulation of RhoGTPases such as RhoA is required at the cell leading edge to achieve cell migration. p190RhoGAP (p190A) is the main negative regulator of RhoA and localizes to membrane protrusions, where its GTPase-activating protein (GAP) activity is required for directional migration. In this study, we investigated the molecular processes responsible for p190A targeting to actin protrusions. By analyzing the subcellular localization of truncated versions of p190A in hepatocellular carcinoma cells, we identified a novel functional p190A domain: the protrusion localization sequence (PLS) necessary and sufficient for p190A targeting to leading edges. Interestingly, the PLS is also required for the negative regulation of p190A RhoGAP activity. Further, we show that the F-actin binding protein cortactin binds the PLS and is required for p190A targeting to protrusions. Lastly, we demonstrate that cancer-associated mutations in PLS affect p190A localization and function, as well as tumor cell migration. Altogether, our data unveil a new mechanism of regulation of p190A in migrating tumor cells.

scholarly journals MnSOD mediates shear stress-promoted tumor cell migration and adhesion

2018 ◽  
Vol 129 ◽  
pp. 46-58 ◽  
Author(s):  
Shijun Ma ◽  
Afu Fu ◽  
Sierin Lim ◽  
Geraldine Giap Ying Chiew ◽  
Kathy Qian Luo
Keyword(s):  
Shear Stress ◽  
Cell Migration ◽  
Tumor Cell ◽  
Tumor Cell Migration

scholarly journals WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility

2015 ◽  
Vol 208 (7) ◽  
pp. 961-974 ◽  
Author(s):  
Michael Howell ◽  
Howard Brickner ◽  
Violaine D. Delorme-Walker ◽  
Justin Choi ◽  
Jean-Michel Saffin ◽  
...  
Keyword(s):  
Cell Migration ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mammalian Cells ◽  
Morphological Changes ◽  
Leading Edge ◽  
Heat Shock Protein 90 ◽  
Binding Partner ◽  
Directed Cell Migration ◽  
Essential Function

We previously identified Waf1 Cip1 stabilizing protein 39 (WISp39) as a binding partner for heat shock protein 90 (Hsp90). We now report that WISp39 has an essential function in the control of directed cell migration, which requires WISp39 interaction with Hsp90. WISp39 knockdown (KD) resulted in the loss of directional motility of mammalian cells and profound changes in cell morphology, including the loss of a single leading edge. WISp39 binds Coronin 1B, known to regulate the Arp2/3 complex and Cofilin at the leading edge. WISp39 preferentially interacts with phosphorylated Coronin 1B, allowing it to complex with Slingshot phosphatase (SSH) to dephosphorylate and activate Cofilin. WISp39 also regulates Arp2/3 complex localization at the leading edge. WISp39 KD-induced morphological changes could be rescued by overexpression of Coronin 1B together with a constitutively active Cofilin mutant. We conclude that WISp39 associates with Hsp90, Coronin 1B, and SSH to regulate Cofilin activation and Arp2/3 complex localization at the leading edge.

765: Modified Expression of Heat Shock Protein 27 in Renal Cell Carcinoma

2004 ◽  
Vol 171 (4S) ◽  
pp. 203-203
Author(s):  
Cecilia Sarto ◽  
Paolo Favini ◽  
Cristina Valsecchi ◽  
Stefano Casellato ◽  
Fulvio Magni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Heat Shock Protein 27

Protektive Wirkung von Heat Shock Protein 27 in der Magenmukosa

2005 ◽  
Vol 43 (05) ◽  
Author(s):  
M Ebert ◽  
C Schäfer ◽  
J Hoffmann ◽  
C Kubisch ◽  
G Treiber ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 27 ◽  
Protektive Wirkung
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