Arl13b Regulates Breast Cancer Cell Migration and Invasion by Controlling Integrin-Mediated Signaling

Casalou, Cristina; Faustino, Alexandra; Silva, Fernanda; Ferreira, Inês C.; Vaqueirinho, Daniela; Ferreira, Andreia; Castanheira, Pedro; Barona, Teresa; Ramalho, José S.; Serpa, Jacinta; Félix, Ana; Barral, Duarte C.

doi:10.3390/cancers11101461

Cited by 15 publications

(18 citation statements)

References 38 publications

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“…Recently, our group found evidence that ARL13B plays a role in breast tumorigenesis and cancer progression, likely independently of cilia. Indeed, depletion of ARL13B in breast cancer cells leads to a reduction in cell migration and invasion in vitro and impaired tumor progression in vivo (Casalou et al, 2019). Moreover, our results revealed a new mechanism to explain the role of ARL13B in tumor progression, through the modulation of cell-ECM adhesion and integrin-mediated signaling.…”

Section: Arl13bmentioning

confidence: 62%

“…In the same study, we found that NMIIA mediates ARL13B binding to actin and that both proteins are required for the formation of circular dorsal ruffles (CDRs), which are actin-rich structures required for cell migration (Casalou et al, 2014). Our group also found that GTP-bound ARL13B interacts with NMIIA in breast cancer cells (Casalou et al, 2019). Other studies reported the role of NMIIA in different types of cancers and indicate that NMIIA can function as a tumor suppressor or oncogene.…”

Section: Arl13bmentioning

confidence: 64%

“…Indeed, several types of cancer exhibit differential expression and/or activation of NMII isoforms, leading to alterations in cell migration and invasion that are involved in tumorigenesis (Newell-Litwa et al, 2015). Moreover, we found that NMIIA is an effector of ARL13B (Casalou et al, 2014(Casalou et al, , 2019. Furthermore, blebbistatin inhibits the ATPase activity of NMIIA and has been found to block invasiveness of both breast cancer cells (Derycke et al, 2011) and pancreatic adenocarcinoma cells (Duxbury et al, 2004), and is phototoxic in human cancer cells under exposure to blue light (Mikulich et al, 2012).…”

Section: Therapeutic Strategiesmentioning

confidence: 80%

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The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

Casalou

Ferreira

Barral

2020

Front. Cell Dev. Biol.

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The Adenosine diphosphate-Ribosylation Factor (ARF) family belongs to the RAS superfamily of small GTPases and is involved in a wide variety of physiological processes, such as cell proliferation, motility and differentiation by regulating membrane traffic and associating with the cytoskeleton. Like other members of the RAS superfamily, ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. Several studies have reported that cancer cells are able to subvert membrane traffic regulators to enhance migration and invasion. Indeed, members of the ARF family, including ARF-Like (ARL) proteins have been implicated in tumorigenesis and progression of several types of cancer. Here, we review the role of ARF family members, their GEFs/GAPs and effectors in tumorigenesis and cancer progression, highlighting the ones that can have a pro-oncogenic behavior or function as tumor suppressors. Moreover, we propose possible mechanisms and approaches to target these proteins, toward the development of novel therapeutic strategies to impair tumor progression.

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Section: Arl13bmentioning

confidence: 62%

Section: Arl13bmentioning

confidence: 64%

Section: Therapeutic Strategiesmentioning

confidence: 80%

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The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

Casalou

Ferreira

Barral

2020

Front. Cell Dev. Biol.

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“…ARL13B was also involved in the GBM development, and the protein level of ARL13B was higher in tumor samples than in normal samples. Casalou et al con rmed that breast cancer was promoted by ARL13B, which was connected with cancer cell migration and invasion [36]. Another gene, SETDB1 regulated histone methylation, gene silencing, and transcriptional repression [37].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers and candidate small molecule drugs in glioblastoma

Xie

Yuan

et al. 2020

Preprint

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Background and aims:Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Methods:Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. Results:A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. Conclusions:Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.

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“…ARL4A could interact with Robo1 to promote cell migration by activating Cdc42 (10). A recent study reveals that ARL13B can enhance the migration and invasion of breast cancer cells via controlling integrin-mediated signaling pathway (11). Moreover, ARL4C overexpression promotes the progression of glioblastoma (GBM) in vitro and in vivo and indicates the poor prognosis for patients with GBM (12).…”

Section: Introductionmentioning

confidence: 99%

ARL4C is A Key Driver of Gastric Cancer: An Integrative Analysis of ARL Family Members

Xie¹,

Bai²,

Lu³

et al. 2020

Preprint

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Background: As small GTP-binding proteins, ARL family members (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive.Methods: The expression status, interactive relations, potential pathways and genetic variations of ARLs are analyzed by bioinformatics tools. Machine learning models and enrichment analysis are performed by R platform. The biological functions of ARL4C are demonstrated by in vitro and in vivo experiments. The nomogram is further constructed to validate the prognostic value of ARL4C for GC patients.Results: ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant diagnostic and prognostic indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably reverses the epithelial-mesenchymal transition (EMT) and inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that TGF-β1 is highly correlated with ARL4C, while ARL4C-related genes are significantly enriched in the TGF-β1 signaling. Correspondingly, we demonstrate that TGF-β1 treatment dramatically increases ARL4C expression, and ARL4C knockdown reverses TGF-β1-induced EMT possibly by inhibiting the expression of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients both in Kaplan-Meier analysis and nomogram model.Conclusion: Our work is of significance for comprehensively understanding the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.

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Arl13b Regulates Breast Cancer Cell Migration and Invasion by Controlling Integrin-Mediated Signaling

Cited by 15 publications

References 38 publications

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

Identification of potential biomarkers and candidate small molecule drugs in glioblastoma

ARL4C is A Key Driver of Gastric Cancer: An Integrative Analysis of ARL Family Members

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