Acetylation of ezrin regulates membrane–cytoskeleton interaction underlying CCL18-elicited cell migration

Song, Xiaoyu; Wang, Wanjuan; Wang, Haowei; Yuan, Xiao; Yang, Fengrui; Zhao, Lingli; Mullen, McKay; Du, Shihao; Zohbi, Najdat; Muthusamy, Saravanakumar; Cao, Yalei; Jiang, Jiying; Xia, Peng; He, Ping; Ding, Mingrui; Emmett, Nerimiah; Ma, Mingming; Wu, Qiulian; Green, Hadiyah-Nicole; Ding, Xia; Wang, Dongmei; Wang, Fengsong; Liu, Xing

doi:10.1093/jmcb/mjz099

Cited by 18 publications

(17 citation statements)

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“…Binding to specific interaction partners might contribute to ERM-1 localization, but alternative mechanisms of regulation are also possible. For example, a recent study found that in breast epithelial cells, ezrin membrane association is regulated by acetylation of ezrin (Song et al, 2019). Overall, these results demonstrate that C-terminal phosphorylation is a versatile regulatory modification that modulates ERM-1 function in a context-dependent manner and underscore the importance of studying ERM regulation in different biological scenarios.…”

Section: Discussionmentioning

confidence: 60%

C-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during Caenorhabditis elegans development

et al. 2020

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ERM proteins are conserved regulators of cortical membrane specialization that function as membrane-actin linkers and molecular hubs. The activity of ERM proteins requires a conformational switch from an inactive cytoplasmic form into an active membrane- and actin-bound form, which is thought to be mediated by sequential PIP2 binding and phosphorylation of a conserved C-terminal threonine residue. Here, we use the single Caenorhabditiselegans ERM ortholog, ERM-1, to study the contribution of these regulatory events to ERM activity and tissue formation in vivo. Using CRISPR/Cas9-generated erm-1 mutant alleles, we demonstrate that a PIP2-binding site is crucially required for ERM-1 function. By contrast, dynamic regulation of C-terminal T544 phosphorylation is not essential but modulates ERM-1 apical localization and dynamics in a tissue-specific manner, to control cortical actin organization and support lumen formation in epithelial tubes. Our work highlights the dynamic nature of ERM protein regulation during tissue morphogenesis and the importance of C-terminal phosphorylation in fine-tuning ERM activity in a tissue-specific context.

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Section: Discussionmentioning

confidence: 60%

C-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during Caenorhabditis elegans development

et al. 2020

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“…Identification of HCC migration inhibitors using natural products from Chinese herbs. Recent study unraveled the importance of ezrin protein acetylation in CCL18-elicited breast cancer metastasis 32 . Since our early study revealed the role of ezrin Thr567 phosphorylation in promoting intra-hepatocellular metastasis in xenografts and ezrin T567 phosphorylation in a context-dependent manner 20 , we sought to screen inhibitors to prevent the intra-hepatocellular carcinoma metastasis.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies showed that ezrin and its interaction partner ACAP4 acetylation is involved in breast cancer metastasis in response to cytokine CCL18 stimulation 32,58 . Given the hyper-activation of Aurora kinase activity in HCC 59 , acetyl-phosphorylation cross-talk on the regulation of cellular dynamics 60 , it would be of great interest to delineate the spatiotemporal dynamics of ezrin acetylation and ROCK2-mediated phosphorylation in HCC metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…1C). To quantitatively evaluate the celastrol effects on cell migration, the migration velocity (υT) and directional migration velocity (υD) of MHCC97H cells were calculated as done previously 32,33 . υT representing the cell migration velocity, while υD representing the directional migration velocity (Fig.…”

Section: Cytotoxic Effect Of Celastrol On Hepatocellular Carcinoma Cementioning

confidence: 99%

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Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells

Song

et al. 2020

Sci Rep

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Chemicals and antibody. Celastrol was ordered from MedChemExpress under the item number HY-13067. Antibodies against ezrin, ezrin pT567 and α-tubulin (DM1A) were purchased from Cell Signaling Technology. Antibodies against ROCK2 and ROCK2 (phospho S1366) were purchased from Abcam. Anti-GFP antibodies were purchased from Santa Cruz Biotechnology. Anti-FLAG-tag (M2) antibody was from Sigma. plasmids. The development of bacterial expression vectors containing human ezrin fused to histidine was described previously 61. EGFP-tagged ezrin plasmids was produced as described before 62. PCR amplified ROCK2 cDNA was cloned into the 3× FLAG-Myc-CMV-24 vector (Sigma) by BamHI and RcoRI digestion. The mutanted of ezrin and ROCK2 were constructed by Fast Mutagenesis Kit (Vazyme Biotech). All plasmids were verified by sequencing (Tsingke Biological Tech). cell culture and transfection. MHCC97H was a gift from Professor Yong Chen (Fourth Military Medical University) 20. HepG2 and HEK293T cells were from American Type Culture Collection (ATCC). Huh7 cells were from National Infrastructure of Cell Line Resource. The cells were incubated according to ATCC instruction. Cells were transfected using conventional calcium phosphate method or the Lipofectamine 3,000 (Invitrogen) according to manufacturer's instructions. Determination of cell viability (MTS assay). Celastrol cytotoxicity was assessed with the use of a CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega), which is a form of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay. Cells (5,000 cells/well) were plated in 96-well plates, treated with various concentrations of celastrol for 24 h. After celastrol treatment, cell viability was determined by adding a small amount of the One Solution Reagent directly to culture wells, incubating for 3 h and then recording the absorbance at 490 nm with a 96-well plate reader. Wound healing assay. MHCC97H, HepG2 or Huh7 cells with logarithmic growth phases, was cultivated in 12 orifices with 5 × 10 5 cells density. Each group has three replicates. After a starvation of 6 h in serum-free medium, 10 μl Tip was taken to vertical scratch "#" glyph at the bottom of the culture plate. The floating cells were washed off with PBS and the celastrol was dissolved in medium supplemented with 20% FBS. Samples were photographed at 0 h, 4 h and 8 h. Image J software was used to measure and compare the effects of celastrol on cell migration. Single cell tracking assay. The cell migration by single cell tracking assay was performed as previously described 32. Briefly, MHCC97H cells were laid in a Silian dish. After stabilized, the cells were starved with Opti-MEM for 6 h, and then cultured in DMEM containing 20% FBS. The movement track of 10 single-cells in each field of view were recorded by microscope for 6 h, with 10 min interval at once.

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“…62 In addition to the fact that αvβ3 directly enhances PCa invasion via chemokine-mediated processes, membrane dynamics are also involved in the migration of malignant tumors induced by chemokines. [63][64][65] Integrin αvβ3 directly interacts with the ECM. In addition, actin rearrangement also plays a key role in regulating cellular interactions with the ECM, such as motility and vesicular trafficking.…”

Section: Cellular Chemokines Can Enhance Pca Invasion By Regulating αmentioning

confidence: 99%

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

Tang¹,

Xu²,

Zhang³

et al. 2020

OTT

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In prostate cancer, distant organ metastasis is the leading cause of patient death. Although the mechanism of malignant tumor metastasis is unclear, studies have confirmed that integrin αVβ3 plays an important role in this process. In prostate cancer, αVβ3 mediates adhesion, invasion, immune escape and neovascularization through interactions with different ligands. Among these ligands and in addition to proteins that are directly related to tumor invasion, other proteins that contain the RGD structure could also bind to αVβ3 and cause a number of biological effects. In this article, we summarized the ligand and downstream proteins related to αVβ3-mediated prostate cancer metastasis as well as some diagnostic and therapeutic measures targeting αVβ3.

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Acetylation of ezrin regulates membrane–cytoskeleton interaction underlying CCL18-elicited cell migration

Cited by 18 publications

References 53 publications

C-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during Caenorhabditis elegans development

C-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during Caenorhabditis elegans development

Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells

<p>Role of αVβ3 in Prostate Cancer: Metastasis Initiator and Important Therapeutic Target</p>

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