ErbB4‐mediated regulation of vasculogenic mimicry capability in breast cancer cells

Kawahara, Ryota; Simizu, Siro

doi:10.1111/cas.15258

Cited by 7 publications

(4 citation statements)

References 46 publications

(105 reference statements)

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“…Horseradish peroxidase‐conjugated sheep polyclonal anti‐mouse IgG (GE Healthcare Life Sciences, Chicago, IL) was used as a secondary antibody. Signals were detected using Immobilon Western Chemiluminescent HRP substrate (Merck KGaA) [ 24 , 25 ]. Protein bands were quantified in ImageJ (National Institutes of Health, Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

et al. 2023

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C‐mannosylation is a rare type of protein glycosylation whereby a single mannose is added to the first tryptophan in the consensus sequence Trp‐Xaa‐Xaa‐Trp/Cys (in which Xaa represents any amino acid). Its consensus sequence is mainly found in proteins containing a thrombospondin type‐1 repeat (TSR1) domain and in type I cytokine receptors. In these proteins, C‐mannosylation affects protein secretion, intracellular localization, and protein stability; however, the role of C‐mannosylation in proteins that are not type I cytokine receptors and/or do not contain a TSR1 domain is less well explored. In this study, we focused on human vitelline membrane outer layer protein 1 homolog (VMO1). VMO1, which possesses two putative C‐mannosylation sites, is a 21‐kDa secreted protein that does not contain a TSR1 domain and is not a type I cytokine receptor. Mass spectrometry analyses revealed that VMO1 is C‐mannosylated at Trp105 but not at Trp44. Although C‐mannosylation does not affect the extracellular secretion of VMO1, it destabilizes the intracellular VMO1. In addition, a structural comparison between VMO1 and C‐mannosylated VMO1 showed that the modification of the mannose changes the conformation of three loops in VMO1. Taken together, our results demonstrate the first example of C‐mannosylation for protein destabilization of VMO1.

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Section: Methodsmentioning

confidence: 99%

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

et al. 2023

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“…Establishment of DPY19L3-knockout cell lines using the CRISPR/Cas9 system DPY19L3-knockout (KO) HT1080 cell line was formed with the CRISPR/Cas9 system using formerly reported methods [18,19]. The oligos that were used to create single-guide RNA (sgRNA) were inserted into the BbsI site of the pSpCas9n(BB)-2A-Puro (PX459) V2.0 vector, which was placed into Addgene by Dr. Feng Zhang (#62987, Addgene, Cambridge, MA, USA).…”

Section: Cell Culturementioning

confidence: 99%

DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

BAYDOUN,

KATO,

KAMO

et al. 2024

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C -mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C -mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C -mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C -mannosyltransferase, and aimed to unravel its role in VM. Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells. Re-expression of wild-type DPY19L3 recovered VM formation; however, DPY19L3 isoform2, an enzymatic activity-defect mutant, did not restore it, suggesting that the C -mannosyltransferase activity of DPY19L3 is crucial to its function. Furthermore, the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability. Altogether, our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C -mannosylation in oncogenesis.

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“…VM assay was performed as previously described [25,[29][30][31][32]. Briefly, 96-well plates were coated with 40 lL per well of Matrigel Ò Growth Factor Reduced (Corning, Corning, NY, USA) and incubated for 30 min at 37 °C.…”

Section: Vm Assaymentioning

confidence: 99%

Cofilin promotes vasculogenic mimicry by regulating the actin cytoskeleton in human breast cancer cells

2023

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Vasculogenic mimicry (VM) is the formation of microvascular channels by cancer cells. VM requires cellular processes that are regulated by changes in cellular migration and morphology. Cofilin (CFL), a key regulator of actin depolymerization, has been reported to affect malignant phenotypes of cancer. We show that treatment with inhibitors of actin dynamics suppresses VM in MDA-MB-231 human breast cancer cells. We established CFL-knockout (KO) MDA-MB-231 cells and found that VM was attenuated in CFL-KO cells. Although the re-expression of wild-type CFL restored VM in CFL-KO cells, inactive phosphomimetic CFL failed to do so. Collectively, our results demonstrate that CFL is a critical regulator of VM and implicate CFL as a novel therapeutic target for breast cancer.

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ErbB4‐mediated regulation of vasculogenic mimicry capability in breast cancer cells

Cited by 7 publications

References 46 publications

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C‐mannosylation

DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity

Cofilin promotes vasculogenic mimicry by regulating the actin cytoskeleton in human breast cancer cells

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