Effects of Arf6 downregulation on biological characteristics of human prostate cancer cells

Lei, Haiming; Ma, Feifei; Jia, Renfeng; Tan, Bo

doi:10.1590/s1677-5538.ibju.2019.0499

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The possibly strongest of these changes were the increases in apoptosis and cell death. Previous evidence for ARF6-mediated suppression of apoptosis and cell death is limited, but available from prostate cancer cells, T cells, glioblastoma and osteosarcoma cells, and Caenorhabditis elegans, and included suppression of apoptosis and nonapoptotic cell death by ARF6 (Bhanot et al, 2010;Kutscher et al, 2018;Lei et al, 2020;Sumiyoshi et al, 2021). Cell death in annexin Vpositive/7-AAD-positive cells detected in our flowcytometry analyses may result either from apoptosis or necrosis.…”

Section: Discussionmentioning

confidence: 99%

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

et al. 2021

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The presumed ARF6 inhibitor NAV2729 inhibits human prostate smooth muscle contraction and proliferation of stromal cells, which are driving factors of voiding symptoms in benign prostatic hyperplasia (BPH). However, its specificity and a confirmed role of ARF6 for smooth muscle contraction are still pending. Here, we generated monoclonal ARF6 knockouts in human prostate stromal cells (WPMY-1), and characterized phenotypes of contractility, growth-related functions, and susceptibility to NAV2729 in knockout and control clones.ARF6 knockout was verified by Western blot. Knockout clones showed impaired contraction and actin organization, reduced proliferation and viability, and increased apoptosis and cell death. In ARF6-expressing control clones, NAV2729 (5 µM) strongly inhibited contraction (67% inhibition accross all three control clones), actin organization (72%), proliferation (97%) and viability (up to 82%), and increased apoptosis (5-fold) and cell death (6-fold). In ARF6 knockouts, effects of NAV2729 (5 µM) were widely reduced, including lacking or minor effects on contractions (0% inhibition accross all three knockout clones), actin (18%) and proliferation (13%), and lacking increases of apoptosis and cell death. Viability was reduced by NAV2729 with an IC 50 of 3.3 µM across all three ARF6 control clones, but of 4.5-8.2 µM in ARF6 knockouts. In conclusion, ARF6 promotes prostate smooth muscle contraction and proliferation of stromal cells. Both are inhibited by NAV2729, which showed high specificity for ARF6 up to 5 µM and represents an attractive compound in the context of BPH.Considering the relevance of smooth muscle-based diseases, shared roles of ARF6 in other smooth muscle types merit further investigation.

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Section: Discussionmentioning

confidence: 99%

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

et al. 2021

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“…Importantly we also found that ARF6 took part in the above process (regulation of small GTPase mediated signal transduction, regulation of actin cytoskeleton, and mediating focal adhesion signal pathway), which means that ARF6 is closely related to the main biological functions of RAC1. It has been reported that down-regulation expression of ARF6 in vitro might inhibit the invasion, migration and proliferation of prostate cancer cells through ERK1/2 phosphorylation and down-regulation expression of RAC1 [97]. Recent study [98]have found that the deletion of Pals1 in colorectal cancer cells increased the activity of ARF6 and RAC1, which further led to the enhanced cell migration in vitro, and the increased metastasis of transplanted tumor cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

RAC1: Comprehensive Analysis of Genetic Alteration, Prognostic and Immunological Role Over Tumor Profiles

Wang

et al. 2022

Preprint

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Background RAC1 is involved in many physiological processes such as cytoskeleton regulation, and is highly related to the occurrence and development of various tumors. The global characterization of RAC1 in different tumor backgrounds is necessary to understand the mechanism of RAC1 involved in tumor progression Methods Based on the data of The Cancer Genome Atlas (TCGA), Gene Expression Omnibu (GEO), Human Protein Atlas (HPA), Genotype-Tissue Expression (GTEx) and so on, this paper comprehensively expounded the expression and prognosis of RAC1 in different tumors, and further analyzed the effects of genetic changes (gene mutation, epigenetic changes) of RAC1 on expression and immune infiltration on prognosis. Results RAC1 was highly expressed in most tumors and was associated with poor prognosis. Gene mutation, alternative splicing events and methylation of RAC1 may affect the abnormal expression of RAC1 in tumors. Interestingly, we found that RAC1-related immune cell infiltration was consistent between endothelial cells and fibroblasts, and RAC1-related macrophage infiltration in LIHC and LUAD was consistent with poor patient outcomes. Conclusions We have enriched the tumor-promoting role of RAC1 in different tumor profiles as a whole and speculated the intrinsic link, providing a basis for the search for potential biomarker.

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Reprogramming of Cell Death Pathways by Bacterial Effectors as a Widespread Virulence Strategy

2022

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Effects of Arf6 downregulation on biological characteristics of human prostate cancer cells

Cited by 3 publications

References 23 publications

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

RAC1: Comprehensive Analysis of Genetic Alteration, Prognostic and Immunological Role Over Tumor Profiles

Reprogramming of Cell Death Pathways by Bacterial Effectors as a Widespread Virulence Strategy

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