Cooperative recruitment of Arl4A and Pak1 to the plasma membrane contributes to sustained Pak1 activation for cell migration

Chen, Kuan‐Jung; Chiang, Tsung‐Yu; Yu, Chia‐Jung; Lee, Fang‐Jen S.

doi:10.1242/jcs.233361

Cited by 11 publications

(12 citation statements)

References 65 publications

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“…In our study, the increased ECP suggested a poor prognosis of OCSCC, which was in line with the qRT-PCR results that showed higher expression of ECP (RNASE3) in oral cancer cell line. ADP-ribosylation factor (Arf)-like 4D (ARL4D) is an Arf-like small GTPase that regulates actin cytoskeleton remodeling, cell morphology and migration [ 24 ]. Lin et al reported that ARL4D plays an important role in microtubule growth [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma

et al. 2021

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RNA binding proteins (RBPs) play a pivotal role in various biological processes, and aberrant expression of RBPs is closely associated with tumorigenesis and progression. However, the role of RBPs in oral cavity squamous cell carcinoma (OCSCC) is yet unveiled. In this study, RNA sequences and clinical information of OCSCC samples were acquired from The Cancer Genome Atlas (TCGA) database. A total of 650 RBPs, with significantly different expression between healthy and OCSCC samples, were identified using the limma package. A prognostic model was constructed by Lasso-Cox analysis, resulting in the determination of 7 prognosis-related RBPs: ERMP1, RNASE3, ARL4D, CSRP2, ULK1, ZC3H12D, and RPS28. Based on the prognostic model, the risk scores of the OCSCC samples were calculated. The capability of the prognostic model was further evaluated using the receiver operating characteristic curve (ROC). The areas under ROC were 0.764, 0.771, and 0.809 at 1, 3 and 5-year respectively in the TCGA dataset. Internal and external validation showed satisfactory predictive capability for prognosis in OCSCC. In addition, a nomogram was created to graphically present the model. To further validate the analytical data, qRT-PCR was performed on normal and OCSCC cell lines. The mRNA expression of the 7 prognostic genes was in accordance with the analytical results. Functional analysis and gene connection networks were used to describe the biological functions and underlying interactions among the 7 prognostic genes Overall, 7 prognosis-related RBPs were identified, which could be used to predict clinical prognosis and to identify potential therapeutic targets for OCSCC.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma

et al. 2021

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“…Cooperative recruitment of Arl4A and Pak1 to the plasma membrane contributes to sustained Pak1 activation for cell migration [32]. Furthermore, the ubiquitination of proteins has been found to be involved in the cancer process.…”

Section: Discussionmentioning

confidence: 99%

Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma

Qiu

Chen

et al. 2020

Cancer Cell Int

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Background: Osteosarcoma (OS) is a common primary malignant bone tumour. Growing evidence suggests that circular RNAs (circRNAs) are closely related to the development of tumours. However, the function of circRNAs in OS remains unknown. Here, we aimed to determine the regulatory mechanisms of circRNAs in OS. Methods:The expression profiles of OS circRNA (GSE96964), microRNA (GSE65071) and mRNA (GSE33382) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNAs, miRNAs and mRNAs in OS. A ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. MRNAs with significant prognostic differences were identified by the TARGET database in the network. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. Results:A total of 15 downregulated circRNAs, 136 upregulated miRNAs and 52 downregulated mRNAs were identified in OS. Finally, a circRNA-miRNA-mRNA network was constructed in OS based on 14 circRNAs, 24 miRNAs, and 52 mRNAs. GO and KEGG pathway analyses suggested that the mRNAs in the network may be involved in the pathogenesis and progression of OS. Four mRNAs identified by the TARGET database were significantly associated with OS survival prognosis. A circRNA-miRNA-mRNA subnetwork was constructed based on these four mRNAs. Conclusion:Our results provide a deeper understanding of the regulatory mechanisms by which circRNAs compete for endogenous RNAs in OS.

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“…Western blotting was performed as described previously ( Chen et al, 2020 ). After washing, the membranes were developed using an enhanced chemiluminescence system (Millipore).…”

Section: Methodsmentioning

confidence: 99%

AMPK promotes Arf6 activation in a kinase-independent manner upon glucose starvation

Chen

Hsu

Lee

2022

Journal of Cell Science

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AMP-activated protein kinase (AMPK) is a crucial cellular nutrient and energy sensor that maintains energy homeostasis. AMPK also governs cancer cell invasion and migration by regulating gene expression and activating multiple cellular signaling pathways. ADP-ribosylation factor 6 (Arf6) can be activated via nucleotide exchange by guanine nucleotide exchange factors (GEFs), and its activation also regulates tumor invasion and migration. By studying GEF-mediated Arf6 activation, we elucidated that AMPK functions as a noncanonical GEF for Arf6 in a kinase-independent manner. Moreover, by examining the physiological role of the AMPK-Arf6 axis, we determined that AMPK activates Arf6 upon glucose starvation and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) treatment. We further identified the binding motif in the C-terminal regulatory domain of AMPK that is responsible for promoting Arf6 activation and thus inducing cell migration and invasion. These findings reveal a noncanonical role of AMPK in which its C-terminal regulatory domain serves as a GEF for Arf6 during energy deprivation.

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Cooperative recruitment of Arl4A and Pak1 to the plasma membrane contributes to sustained Pak1 activation for cell migration

Cited by 11 publications

References 65 publications

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma

Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma

Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma

AMPK promotes Arf6 activation in a kinase-independent manner upon glucose starvation

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