The Rho/Rho-kinase and the phosphatidylinositol 3-kinase pathways are essential for spontaneous locomotion of Walker 256 carcinosarcoma cells

Wicki, Andreas; Niggli, Verena

doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1128>3.0.co;2-b

Cited by 25 publications

(18 citation statements)

References 41 publications

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“…Recent findings in our laboratory revealed that activities of Rho and Rho-kinase are essential for polarization and migration in these cells, as inhibition of Rho with C3 exoenzyme and Rho-kinase with Y-27632 abrogated cell polarity and migration. Rho-kinases are predominantly located in the membrane fraction in Walker carcinosarcoma cells, indicative of their constitutive activation [23]. The downstream targets of Rho/Rho-kinase have not yet been elucidated in this cell line.…”

Section: Introductionmentioning

confidence: 68%

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Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells

Gutjahr

Rossy

Niggli

2005

Experimental Cell Research

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Section: Introductionmentioning

confidence: 68%

“…As shown previously [23], the Rho inhibitor C3 exoenzyme, which specifically inhibits RhoA, RhoB, and RhoC, suppressed polarization by 94% (Figs. 2Ad, B) and migration by 90% ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells

Gutjahr

Rossy

Niggli

2005

Experimental Cell Research

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“…Among these we should mention NCOA1 (nuclear receptor coactivator (1), a transcriptional coactivator belonging to the SRC family which is deregulated in breast and prostatic cancer and may potentiate gene expression by acting as a coactivator for nuclear hormone receptors and other transcription factors (TF) [44][45][46][47][48][49][50][51][52][53][54][55]; and ROCK2, a serine/threonine kinase member of the Rho pathway, involved in cell adhesion, migration, invasion, and mitosis [56][57][58][59], which may be a potential therapeutic target in human cancer cells and animal models [60][61][62][63][64][65][66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Chromosome 2p gain in monoclonal B‐cell lymphocytosis and in early stage chronic lymphocytic leukemia

et al. 2012

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Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P 5 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 3 10 24 ) and CD38 (P < 1 3 10 24 ) and ZAP-70 positive expression (P 5 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P 5 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P 5 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion. Am. J. Hematol. 88:24-31, 2013. V

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“…Positive-feedback loops have been implicated in spontaneous polarization of PI3K signaling and random migration in cells that exhibit amoeboid motility (neutrophils and Dictyostelium discoideum), although in those contexts F-actin is required for maintaining PI3K activation Xu et al, 2003). In certain transformed cells, constitutive membrane localization of PI3K has been implicated in spontaneous cell polarization and migration (Wicki and Niggli, 2001).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts

Weiger

Wang

Krajcovic

et al. 2009

Journal of Cell Science

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During directed cell migration (chemotaxis), cytoskeletal dynamics are stimulated and spatially biased by phosphoinositide 3-kinase (PI3K) and other signal transduction pathways. Live-cell imaging using total internal reflection fluorescence (TIRF) microscopy revealed that, in the absence of soluble cues, 3Ј-phosphoinositides are enriched in a localized and dynamic fashion during active spreading and random migration of mouse fibroblasts on adhesive surfaces. Surprisingly, we found that PI3K activation is uncoupled from classical integrin-mediated pathways and feedback from the actin cytoskeleton. Inhibiting PI3K significantly impairs cell motility, both in the context of normal spreading and when microtubules are dissociated, which induces a dynamic protrusion phenotype as seen by TIRF in our cells. Accordingly, during random migration, 3Ј-phosphoinositides are frequently localized to regions of membrane protrusion and correlate quantitatively with the direction and persistence of cell movement. These results underscore the importance of localized PI3K signaling not only in chemotaxis but also in basal motility/migration of fibroblasts. Journal of Cell Science 314 is largely PI3K dependent. This is seen most dramatically when microtubules are depolymerized using nocodazole, which induces rapid protrusion-retraction events as seen by TIRF. In the context of random fibroblast migration, formation of branched lamellipodia and turning events were found to coincide with localized enrichment of 3Ј-phosphoinositides. Results PI3K lipid products accumulate in a dynamic fashion during fibroblast spreadingTo assess the activation of PI3K signaling and its possible relation to adhesion-based motility, we established stable expression of the 3Ј-phosphoinositide-specific Akt pleckstrin-homology domain, fused with enhanced green fluorescent protein (EGFP-AktPH) in NIH3T3 fibroblasts and monitored these cells by TIRF microscopy as they attached and spread on glass coated with fibronectin or poly-D-lysine (Fig. 1). Glass coated with bovine serum albumin, which was also present in our imaging buffer, does not promote adhesion of these cells (results not shown). After allowing the cells to spread for 30-50 minutes, a saturating dose of PDGF was added to evaluate the maximal activation of PI3K in each cell, followed by a large dose of PI3K inhibitor to evaluate the fluorescence intensity associated with EGFP-AktPH in the cytosol; the latter is used to normalize the PI3K-dependent response (Schneider and Haugh, 2004).Cells spreading on fibronectin consistently showed dynamic enrichment of 3Ј-phosphoinositides, with transient bursts of signaling that were often localized in actively protruding regions at the cell periphery and other times showed a more global pattern ( Fig. 1A; supplementary material Movie 1). These patterns of PI3K signaling are distinct from the more stable, ring-like patterns seen in response to PDGF stimulation, which we have previously explained in quantitative detail (Schneider and Haugh, 2004). Analysis of a...

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The Rho/Rho-kinase and the phosphatidylinositol 3-kinase pathways are essential for spontaneous locomotion of Walker 256 carcinosarcoma cells

Cited by 25 publications

References 41 publications

Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells

Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells

Chromosome 2p gain in monoclonal B‐cell lymphocytosis and in early stage chronic lymphocytic leukemia

Spontaneous phosphoinositide 3-kinase signaling dynamics drive spreading and random migration of fibroblasts

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