The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion by inhibition of Rac activity

Thuault, Sylvie; Comunale, Franck; Hasna, Jessy; Fortier, Mathieu; Planchon, Damien; Elarouci, Nabila; Reyniès, Aurélien de; Bodin, Stéphane; Blangy, Anne; Gauthier-Rouvière, Cécile

doi:10.1091/mbc.e16-01-0041

Cited by 31 publications

(33 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, ARHGAP25, which inhibits Rac activity, is upregulated in FPRMS and its knockdown inhibits invasion. Thus, ROCK acts in FPRMS by upregulating ARHGAP25 and subsequently inhibiting Rac function, which subsequently promotes motility and cellular invasion [84].…”

Section: G Protein and G Protein-coupled Receptorsmentioning

confidence: 99%

Signaling pathways in Rhabdomyosarcoma invasion and metastasis

Ramadan

Fahs

Ghayad

et al. 2020

Cancer Metastasis Rev

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is an aggressive childhood mesenchymal tumor with two major molecular and histopathologic subtypes: fusion-positive (FP)RMS, characterized by the PAX3-FOXO1 fusion protein and largely of alveolar histology, and fusion-negative (FN)RMS, the majority of which exhibit embryonal tumor histology. Metastatic disease continues to be associated with poor overall survival despite intensive treatment strategies. Studies on RMS biology have provided some insight into autocrine as well as paracrine signaling pathways that contribute to invasion and metastatic propensity. Such pathways include those driven by the PAX3-FOXO1 fusion oncoprotein in FPRMS and signaling pathways such as IGF/RAS/MEK/ERK, PI3K/AKT/mTOR, cMET, FGFR4, and PDGFR in both FP and FNRMS. In addition, specific cytoskeletal proteins, G protein coupled receptors, Hedgehog, Notch, Wnt, Hippo, and p53 pathways play a role, as do specific microRNA. Paracrine factors, including secreted proteins and RMS-derived exosomes that carry cargo of protein and miRNA, have also recently emerged as potentially important players in RMS biology. This review summarizes the known factors contributing to RMS invasion and metastasis and their implications on identifying targets for treatment and a better understanding of metastatic RMS.

show abstract

Section: G Protein and G Protein-coupled Receptorsmentioning

confidence: 99%

Signaling pathways in Rhabdomyosarcoma invasion and metastasis

Ramadan

Fahs

Ghayad

et al. 2020

Cancer Metastasis Rev

View full text Add to dashboard Cite

show abstract

“…We identified 1194 genes enriched in ARMS biopsies; 40% of which were in the vicinity of previously identified PAX3FOXO1 bound cis-regulatory modules (CRM) [11,12] (Fig 2B). This list of genes largely comprised previously identified PAX3FOXO1 dependent ARMS markers, such as ALK, ARHGAP25, or FGFR4 [9,47]. Functional annotation of these genes indicated that they encode for developmental regulators of many embryonic lineages known to be dependent on PAX3 and PAX7 activities ( Fig 2C, Table S2) [48], and not exclusively of the muscle lineage.…”

Section: Paxfoxo1 Tfs Convert Chick Neural Cells Into Arms Like-cellsmentioning

confidence: 96%

The PAXFOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

Curto

Vartanian

Frarma

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The chromosome translocations generating PAX3FOXO1 and PAX7FOXO1 chimeric proteins are the primary hallmarks of the paediatric cancer, Alveolar Rhabdomyosarcoma (ARMS).Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAXFOXO1s. Our data demonstrate that PAXFOXO1s, but not wild-type PAX3 and PAX7, trigger the trans-differentiation of neural cells into ARMS-like cells with myogenic characteristics. In parallel expression of PAXFOXO1s remodels the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, gain for PAXFOXO1s, as for wild-type PAX3/7, reduces the levels of CDK-CYCLIN activity and arrests cells in G1. Introduction of CYCLIN D1 or MYCN overcomes PAXFOXO1s mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism underpinning the apparent limited oncogenicity of PAXFOXO1 fusion transcription factors and support a neural origin for ARMS.We deeply thank the ImagoSeine core facility of Institut Jacques Monod, a member of France-BioImaging (ANR-10-INBS-04) and certified IBiSA. We thank Griselda Wentzinger and Magali Fradet for performing cell sorting at ImagoSeine Institut Jacques Monod platform. We are grateful to the people who have provided us with useful tools. We received plasmids from

show abstract

“…Further analysis has revealed that miR-17 directly represses the cell cycle regulator and RB-family member P130 (RB transcriptional co-repressor like 2, RBL2 ), a tumor suppressor that also negatively regulates β-catenin levels and Wnt signaling ( Ma et al, 2012 ). MiR-17 also targets and inhibits PTEN ( Fang et al, 2014 ) and RHOE ( RND3 ), which encodes a GTP-binding protein (without GTPase activity) that is reduced in CRC and can repress tumor cell invasion ( Thuault et al, 2016 ), promote contact inhibition ( Hernández-Sánchez et al, 2015 ) and downregulate Notch signaling ( Tang et al, 2014b ; Zhu et al, 2014b ).…”

Section: The Mir-17 Oncomir Family and Modulation Of Tgf-β Signalingmentioning

confidence: 99%

MicroRNAs in the etiology of colorectal cancer: pathways and clinical implications

Strubberg

Madison

2017

Disease Models &Amp; Mechanisms

120

102

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small single-stranded RNAs that repress mRNA translation and trigger mRNA degradation. Of the ∼1900 miRNA-encoding genes present in the human genome, ∼250 miRNAs are reported to have changes in abundance or altered functions in colorectal cancer. Thousands of studies have documented aberrant miRNA levels in colorectal cancer, with some miRNAs reported to actively regulate tumorigenesis. A recurrent phenomenon with miRNAs is their frequent participation in feedback loops, which probably serve to reinforce or magnify biological outcomes to manifest a particular cellular phenotype. Here, we review the roles of oncogenic miRNAs (oncomiRs), tumor suppressive miRNAs (anti-oncomiRs) and miRNA regulators in colorectal cancer. Given their stability in patient-derived samples and ease of detection with standard and novel techniques, we also discuss the potential use of miRNAs as biomarkers in the diagnosis of colorectal cancer and as prognostic indicators of this disease. MiRNAs also represent attractive candidates for targeted therapies because their function can be manipulated through the use of synthetic antagonists and miRNA mimics.

show abstract

The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion by inhibition of Rac activity

Abstract: New molecular pathways involved in alveolar rhabdomyosarcoma aggressiveness are found by identifying the RhoE/ROCK/ARHGAP25 signaling pathway as promoting the invasive potential of alveolar rhabdomyosarcoma.

Cited by 31 publications

References 39 publications

Signaling pathways in Rhabdomyosarcoma invasion and metastasis

Signaling pathways in Rhabdomyosarcoma invasion and metastasis

The PAXFOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

MicroRNAs in the etiology of colorectal cancer: pathways and clinical implications

Contact Info

Product

Resources

About