<scp>R</scp>ho<scp>J</scp> modulates melanoma invasion by altering actin cytoskeletal dynamics

Ho, Hsiang‐Ling; Hopkin, Amelia Soto; Kapadia, Rubina; Vasudeva, Priya; Schilling, Jonathan S.; Ganesan, Anand K.

doi:10.1111/pcmr.12058

Cited by 26 publications

(35 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, RhoJ and Arl4D were validated as genes differentially regulated between C57 and Cav-1 KO and are both implicated in actinmediated cell migration (47,48). Furthermore, Cxcr4 was also validated as a differentially regulated gene and is implicated in dopaminergic cell migration (49).…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

While glucocorticoids (GCs) are used clinically to treat many conditions, their neonatal and prenatal usage is increasingly controversial due to reports of delayed adverse outcomes, especially their effects on brain development. Such alterations may reflect the impact of GCs on neural progenitor/stem cell (NPSC) function. We previously demonstrated that the lipid raft protein caveolin-1 (Cav-1) was required for rapid GC signaling in embryonic mouse NPSCs operating through plasma membranebound glucocorticoid receptors (GRs). We show here that genomic GR signaling in NPSCs requires Cav-1. Loss of Cav-1 impacts the transcriptional response of many GR target genes (e.g., the serum-and glucocorticoid-regulated kinase 1 gene) that are likely to mediate the antiproliferative effects of GCs. Microarray analysis of wild-type C57 or Cav-1-deficient NPSCs identified approximately 100 genes that are differentially regulated by GC treatment. These changes in hormone responsiveness in Cav-1 knockout NPSCs are associated with the loss of GC-regulated phosphorylation of GR at serine 211 but not at serine 226. Chromatin recruitment of total GR to regulatory regions of target genes such as Fkbp-5, RhoJ, and Sgk-1, as well as p211-GR recruitment to Sgk-1, are compromised in Cav-1 knockout NPSCs. Cav-1 is therefore a multifunctional regulator of GR in NPSCs influencing both rapid and genomic action of the receptor to impact cell proliferation.

show abstract

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Peffer

Chandran

Luthra

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…This is the first report of p41ARC serving as a downstream effector of PAK1 signaling in skeletal muscle cells. PAK1 has been shown to phosphorylate p41ARC in vitro, in MCF-7 cancer cells upon EGF stimulation (24,26), and in melanoma cells (25). p41ARC is one of two principle ARP2/3 subunits, the other and more commonly used subunit being ARPC1A (40).…”

Section: Cytoskeletal Regulation Of Skeletal Muscle Glucose Uptakementioning

confidence: 99%

The actin-related p41ARC subunit contributes to p21-activated kinase-1 (PAK1)–mediated glucose uptake into skeletal muscle cells

Tunduguru

Zhang

Aslamy

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, preclinical diabetes, and progression to type 2 diabetes. GLUT4 recruitment to the plasma membrane of skeletal muscle cells requires F-actin remodeling. Insulin signaling in muscle requires p21-activated kinase-1 (PAK1), whose downstream signaling triggers actin remodeling, which promotes GLUT4 vesicle translocation and glucose uptake into skeletal muscle cells. Actin remodeling is a cyclic process, and although PAK1 is known to initiate changes to the cortical actin-binding protein cofilin to stimulate the depolymerizing arm of the cycle, how PAK1 might trigger the polymerizing arm of the cycle remains unresolved. Toward this, we investigated whether PAK1 contributes to the mechanisms involving the actin-binding and -polymerizing proteins neural Wiskott-Aldrich syndrome protein (N-WASP), cortactin, and ARP2/3 subunits. We found that the actin-polymerizing ARP2/3 subunit p41ARC is a PAK1 substrate in skeletal muscle cells. Moreover, co-immunoprecipitation experiments revealed that insulin stimulates p41ARC phosphorylation and increases its association with N-WASP coordinately with the associations of N-WASP with cortactin and actin. Importantly, all of these associations were ablated by the PAK inhibitor IPA3, suggesting that PAK1 activation lies upstream of these actin-polymerizing complexes. Using the N-WASP inhibitor wiskostatin, we further demonstrated that N-WASP is required for localized F-actin polymerization, GLUT4 vesicle translocation, and glucose uptake. These results expand the model of insulin-stimulated glucose uptake in skeletal muscle cells by implicating p41ARC as a new component of the insulin-signaling cascade and connecting PAK1 signaling to N-WASP-cortactin-mediated actin polymerization and GLUT4 vesicle translocation.

show abstract

“…TCL suppression in these experiments inhibited pro-angiogenic vessel infiltration of tumors and promoted a loss of vessel integrity within the tumor mass (10). TCL expression and activity has also been implicated in metastatic melanomas, conferring both chemo-resistance and enhanced motility to the cancer cells (11,12). These unique niches of TCL activity suggest it is a strong candidate for directed chemotherapy, with few anticipated off-target effects, particularly as TCL knock-out mice show little phenotypic impairments except minor defects in corneal development (10,13).…”

Section: Tcl/rhoj Was First Characterized About 15 Years Ago As a Rhomentioning

confidence: 82%

TCL/RhoJ Plasma Membrane Localization and Nucleotide Exchange Is Coordinately Regulated by Amino Acids within the N Terminus and a Distal Loop Region

Ackermann

Florke

Reyes

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

TCL/RhoJ is a Cdc42-related Rho GTPase with reported activities in endothelial cell biology and angiogenesis, metastatic melanoma, and corneal epithelial cells; however, less is known about how it is inherently regulated in comparison to its closest homologues TC10 and Cdc42. TCL has an N-terminal extension of 18 amino acids in comparison to Cdc42, but the function of this amino acid sequence has not been elucidated. A truncation mutant lacking the N terminus (ΔN) was found to alter TCL plasma membrane localization and nucleotide binding, and additional truncation and point mutants mapped the alterations of TCL biochemistry to amino acids 17-20. Interestingly, whereas the TCL ΔN mutant clearly influenced nucleotide exchange, deletion of the N terminus from its closest homologue, TC10, did not have a similar effect. Chimeras of TCL and TC10 revealed amino acids 121-129 of TCL contributed to the differences in nucleotide loading. Together, these results identify amino acids within the N terminus and a loop region distal to the nucleotide binding pocket of TCL capable of allosterically regulating nucleotide exchange and thus influence membrane association of the protein.

show abstract

RhoJ modulates melanoma invasion by altering actin cytoskeletal dynamics

Cited by 26 publications

References 37 publications

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

Caveolin-1 Regulates Genomic Action of the Glucocorticoid Receptor in Neural Stem Cells

The actin-related p41ARC subunit contributes to p21-activated kinase-1 (PAK1)–mediated glucose uptake into skeletal muscle cells

TCL/RhoJ Plasma Membrane Localization and Nucleotide Exchange Is Coordinately Regulated by Amino Acids within the N Terminus and a Distal Loop Region

Contact Info

Product

Resources

About