Expression of DOCK9 and DOCK11 Analyzed with Commercial Antibodies: Focus on Regulation of Mutually Exclusive First Exon Isoforms

Parrado, Antonio

doi:10.3390/antib9030027

Cited by 5 publications

(4 citation statements)

References 29 publications

(35 reference statements)

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“…It's reported that DOCK9 is highly expressed in various tissues, including the placenta, lungs, brain, uterus, and thyroid [31]. Studies by Hirata et al demonstrated that DOCK9 contributes to the invasiveness of glioblastoma cells through its effect on Rac1 and Cdc42 activities [32].…”

Section: Discussionmentioning

confidence: 99%

Investigating DOCK9 as a Potential Prognostic Marker: Implications for Angiogenesis and Immunity in Esophageal Squamous Cell Carcinoma

Pan

Yang

Dai

et al. 2023

Preprint

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Background Esophageal squamous cell carcinoma (ESCC) remains a significant public health concern worldwide due to its high incidence and mortality rates. Consequently, developing a robust predictive risk model centered on RNA expression and identifying novel target genes in ESCC is paramount. While previous studies have implicated DOCK9 in tumor prognosis, its specific role in ESCC remains to be elucidated. This study aims to investigate the prognostic significance of DOCK9 and its biological functions in ESCC. Methods We reanalyzed RNA microarray datasets (GSE67269, GSE20347, GSE53625) from the Gene Expression Omnibus (GEO) database to identify potential survival-associated genes and assess their expression in ESCC. We also comprehensively analyzed single-cell RNA sequencing (scRNA-seq) data from GSE160269, GSE188990, and The Cancer Genome Atlas (TCGA) ESCC cohorts to explore potential molecular mechanisms. Kaplan-Meier analysis determined the correlation between DOCK9/CD31 and prognosis. Protein expression of DOCK9 in ESCC tissues was examined through immunohistochemistry and Western blot analyses in a small cohort of six ESCC patients. The co-expression of DOCK9 and CD31 was verified using Immunofluorescence (IF) analysis. Additionally, we investigated the functional impact of DOCK9 on human umbilical vein endothelial cells (HUVECs) proliferation, migration, and tube formation using cell counting kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) staining assay, wound-healing assay, and tube formation assay. Results Our study identified 21 genes from GSE67269, GSE20347, and GSE53625 datasets based on differential and univariate COX analyses, enabling us to construct a prognostic risk model for ESCC where DOCK9 plays a central role. DOCK9 expression was markedly lower in cancerous tissues than in ESCC patients' paracancerous tissues. Furthermore, DOCK9 emerged as a survival-related risk factor in ESCC, exhibiting high expression in tumo endothelial cells (TECs) and playing a role in angiogenesis and tumor-associated fibroblasts development. Our immunity analysis suggested that DOCK9 might influence the immune landscape, and the DOCK9/CD31 ratio could serve as an indicator for assessing the response to immunotherapy in ESCC. Functionally, our assays indicated that inhibiting DOCK9 expression curtailed the proliferation, migration, and tube formation of ANG-2-stimulated HUVECs, a process potentially related to the ANG-2/Tie2 axis. Conclusions Our study provides evidence that DOCK9 could serve as a potential prognostic biomarker associated with angiogenesis and immune therapy in esophageal squamous cell carcinoma, thereby opening avenues for improved therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Investigating DOCK9 as a Potential Prognostic Marker: Implications for Angiogenesis and Immunity in Esophageal Squamous Cell Carcinoma

Pan

Yang

Dai

et al. 2023

Preprint

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“…In addition, because the expression of DOCK11 is regulated by age-dependent mechanisms, any age-associated downregulation of DOCK11 in B cells could impact secondary immune responses [28]. Furthermore, DOCK11 mRNA and protein expressions exhibit good correspondence [29], suggesting that regulation of DOCK11 expression could be relatively straightforward. Interestingly, we observed a significant increase in the expression of DOCK11 at both mRNA and protein levels in HBV-infected cells compared with non-infected cells [20].…”

Section: Subcellular Localization and Expression Regulation Of Dock11mentioning

confidence: 99%

Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes

Li,

Murai,

Lyu

et al. 2024

Viruses

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HBV infection is challenging to cure due to the persistence of viral covalently closed circular viral DNA (cccDNA). The dedicator of cytokinesis 11 (DOCK11) is recognized as a guanine nucleotide exchange factor (GEF) for CDC42 that has been reported to be required for HBV persistence. DOCK11 is expressed in both the cytoplasm and nucleus of human hepatocytes and is functionally associated with retrograde trafficking proteins Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with the HBV capsid, in the trans-Golgi network (TGN). This opens an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. DOCK11 also facilitates the association of cccDNA with H3K4me3 and RNA Pol II for activating cccDNA transcription. In addition, DOCK11 plays a crucial role in the host DNA repair system, being essential for cccDNA synthesis. This function can be inhibited by 10M-D42AN, a novel DOCK11-binding peptide, leading to the suppression of HBV replication both in vitro and in vivo. Treatment with a combination of 10M-D42AN and entecavir may represent a promising therapeutic strategy for patients with chronic hepatitis B (CHB). Consequently, DOCK11 may be seen as a potential candidate molecule in the development of molecularly targeted drugs against CHB.

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“…DOCK9 is a CDC42 GEF ( 35 ). It is widely and highly expressed throughout the body, including the brain; however, antibodies against two isoforms of DOCK9 indicated differing expression profiles ( 121 ). The role of DOCK9 in structural remodeling of cells was investigated in HeLa epithelial cells, where its expression reduced elongated cell morphology and led to increased filopodia and membrane ruffling ( 122 ).…”

Section: Biological Function and Disease Associations Of The Dock Gefsmentioning

confidence: 99%

RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors

Thompson

Bitsina

Gray

et al. 2021

Journal of Biological Chemistry

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The human dedicator of cytokinesis (DOCK) family consists of 11 structurally conserved proteins that serve as atypical RHO guanine nucleotide exchange factors (RHO GEFs). These regulatory proteins act as mediators in numerous cellular cascades that promote cytoskeletal remodeling, playing roles in various crucial processes such as differentiation, migration, polarization, and axon growth in neurons. At the molecular level, DOCK DHR2 domains facilitate nucleotide dissociation from small GTPases, a process that is otherwise too slow for rapid spatiotemporal control of cellular signaling. Here, we provide an overview of the biological and structural characteristics for the various DOCK proteins and describe how they differ from other RHO GEFs and between DOCK subfamilies. The expression of the family varies depending on cell or tissue type, and they are consequently implicated in a broad range of disease phenotypes, particularly in the brain. A growing body of available structural information reveals the mechanism by which the catalytic DHR2 domain elicits nucleotide dissociation and also indicates strategies for the discovery and design of high-affinity small-molecule inhibitors. Such compounds could serve as chemical probes to interrogate the cellular function and provide starting points for drug discovery of this important class of enzymes.

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Expression of DOCK9 and DOCK11 Analyzed with Commercial Antibodies: Focus on Regulation of Mutually Exclusive First Exon Isoforms

Cited by 5 publications

References 29 publications

Investigating DOCK9 as a Potential Prognostic Marker: Implications for Angiogenesis and Immunity in Esophageal Squamous Cell Carcinoma

Investigating DOCK9 as a Potential Prognostic Marker: Implications for Angiogenesis and Immunity in Esophageal Squamous Cell Carcinoma

Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes

RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors

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