Paxillin: a crossroad in pathological cell migration

López-Colomé, Ana Marı́a; Lee-Rivera, Irene; Benavides-Hidalgo, Regina; López, Edith

doi:10.1186/s13045-017-0418-y

Cited by 272 publications

(304 citation statements)

References 121 publications

Supporting

Mentioning

289

Contrasting

Unclassified

Order By: Relevance

“…F,G). Additionally, we stained these cells for paxillin, a FA adaptor, and scaffolding protein, which is phosphorylated partially by FAK upon integrin clustering (Lopez‐Colome et al , ). The mean intensity of paxillin was significantly increased by 68% at FAs of HeLa shRITA cells compared to HeLa shGFP cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

et al. 2019

View full text Add to dashboard Cite

RITA, the RBP‐J interacting and tubulin‐associated protein, has been reported to be related to tumor development, but the underlying mechanisms are not understood. Since RITA interacts with tubulin and coats microtubules of the cytoskeleton, we hypothesized that it is involved in cell motility. We show here that depletion of RITA reduces cell migration and invasion of diverse cancer cell lines and mouse embryonic fibroblasts. Cells depleted of RITA display stable focal adhesions (FA) with elevated active integrin, phosphorylated focal adhesion kinase, and paxillin. This is accompanied by enlarged size and disturbed turnover of FA. These cells also demonstrate increased polymerized tubulin. Interestingly, RITA is precipitated with the lipoma‐preferred partner (LPP), which is critical in actin cytoskeleton remodeling and cell migration. Suppression of RITA results in reduced LPP and α‐actinin at FA leading to compromised focal adhesion turnover and actin dynamics. This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of FA through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression.

show abstract

Section: Resultsmentioning

confidence: 99%

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

et al. 2019

View full text Add to dashboard Cite

show abstract

“…S2C-D), indicating complex, additional layers of regulation in response to loss of WRC. Owing to the principal role of paxillin in signaling to adhesion formation and turnover(44), we further analyzed paxillin phosphorylation. Paxillin phosphorylation on tyrosine Y118 is induced upon integrin activation(45) and prominently involved in focal complex formation beneath lamellipodia as well as focal adhesion formation and turnover(46,47).…”

mentioning

confidence: 99%

Loss of Hem1 disrupts macrophage function and impacts on migration, phagocytosis and integrin-mediated adhesion

Stahnke

Döring

Kusch

et al. 2020

Preprint

View full text Add to dashboard Cite

# equal contribution One sentence summaryInterference of Hem1 function in mice and cells uncovers a hitherto unrecognized role in integrinmediated cell adhesion that is crucial for macrophage function and connects to recently discovered immunodeficiencies in patients carrying Hem1 mutations. ABSTRACTThe hematopoietic-specific protein 1 (Hem1) comprises an essential subunit of the WAVE Regulatory Complex (WRC) in immune cells. WRC has a fundamental role in Arp2/3 complex activation and the protrusion of branched actin networks in motile cells.Hem1 deficiency leads to suppression of the entire WRC in immune cells. Defective WRC function in macrophages results in loss of lamellipodia and migration defects. Moreover, phagocytosis, commonly accompanied by lamellipodium protrusion during cup formation, is altered in Hem1 null cells concerning frequency and efficacy. When analyzing cell spreading, adhesion and podosome formation, we found that Hem1 null cells are capable, in principle, of podosome formation and consequently, do not show any quantitative differences in extracellular matrix degradation. Their adhesive behavior, however, was significantly altered. Specifically, adhesion as well as de-adhesion of Hem1 null cells was strongly compromised, likely contributing to the observed reduced efficiency of phagocytosis. In line with this, phosphorylation of the prominent adhesion component paxillin was diminished. Nonhematopoietic somatic cells disrupted in expression for both Hem1 and its ubiquitous orthologue Nckassociated protein 1 (Nap1) or the essential WRC components Sra-1/PIR121 did not only confirm defective paxillin phosphorylation, but also revealed that paxillin turnover in focal adhesions is accelerated in the absence of WRC. Finally, adhesion assays using platelets lacking functional WRC as model system unmasked radically decreased IIb 3 integrin activation.Our results thus demonstrate that WRC-driven actin networks impact on integrin-dependent processes controlling formation and dismantling of different types of cell-substratum adhesion.Cell migration follows an orchestrated sequence of events, a cycle of cell protrusion, adhesion to newly occupied space and contraction to drag the cell body forward. Polymerization of actin filaments (Factin) at the cell front pushes the plasma membrane into the direction of migration, which then attaches to the extracellular substratum via members of the integrin transmembrane receptors family.Cells in metazoan organisms are capable of migrating through complex, 3-dimensional environments and their license keys to different organismal compartments constitute combinations of integrins they carry on their surface, allowing them to specifically adhere to given substrata (1, 2). Once engaged, the integrins dynamically couple to the actin cytoskeleton, which in turn can exert pulling forces through myosin II activation and contraction, culminating in locomotion of the cell body (3-5)Integrins are heterodimeric cell surface receptors that are responsible for cell adhesion duri...

show abstract

“…Paxillin and tensin 3 mRNA and protein levels were reduced in macrophages upon coculture with breast cancer cells, as well as after treatment with miR-375 containing supernatants from apoptotic MCF-7 cells. Paxillin is a focal adhesion adapter protein that, depending on its subcellular localization, can positively or negatively regulate cell migration [147][148][149]. Similarly, tensin 3 acts as a link between the extracellular matrix and the cytoskeleton and functionally contributes to the switch between adhesive and non-adhesive states in cancer cells, including breast cancer [150,151].…”

Section: Guo Et Al Investigated Mechanisms Of Breast Cancer Invasionmentioning

confidence: 99%

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

Syed

Frank

Raue

et al. 2019

Cells

View full text Add to dashboard Cite

MicroRNAs (miRs) significantly contribute to the regulation of gene expression, by virtue of their ability to interact with a broad, yet specific set of target genes. MiRs are produced and released by almost every cell type and play an important role in horizontal gene regulation in the tumor microenvironment (TME). In the TME, both tumor and stroma cells cross-communicate via diverse factors including miRs, which are taking central stage as a therapeutic target of anti-tumor therapy. One of the immune escape strategies adopted by tumor cells is to release miRs as a Trojan horse to hijack circulating or tumor-localized monocytes/macrophages to tune them for pro-tumoral functions. On the other hand, macrophage-derived miRs exert anti-tumor functions. The transfer of miRs from host to recipient cells depends on the supramolecular structure and composition of miR carriers, which determine the distinct uptake mechanism by recipient cells. In this review, we provide a recent update on the miR-mediated crosstalk between tumor cells and macrophages and their mode of uptake in the TME.(TNF-α), and provoke the secretion of pro-inflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-12, IL-23, and TNF-α and reactive nitrogen and oxygen intermediates (RNI, ROI) [5]. In contrast, anti-inflammatory stimuli such as IL-4, IL-13, IL-10, and glucocorticoid or immune complexes (IC) plus LPS induce macrophages to an M2 phenotype. This type is characterized by a decreased production of pro-inflammatory cytokines, increased production of anti-inflammatory cytokines (e.g., IL-10), and factors that mediate immunosuppression and tissue remodeling. M2 macrophages have been divided into further subgroups. The M2a type is generated in response to IL-3 and IL-13, while M2b macrophages respond to immune complexes and Toll-like receptor (TLR) activation. M2c macrophages represent deactivated macrophages that suppress pro-inflammatory cytokines, while the M2d type represents a regulatory macrophage [6] that is often grouped with TAMs [5,7,8]. In line with these varied responses, Janus-faced macrophage functions are largely determined by their microenvironment rather than their genetic imprint [9,10]. In tumors and during the resolution of inflammation, hijacked macrophages attain pro-tumor or wound healing phenotypes due to tumor-derived factors [11], which emerge as a target for tumor therapy [12,13]. TAMs expressing classical activation markers produce pro-inflammatory cytokines and reactive oxygen species (ROS) and, thus, are crucial for tumor cell killing [14,15]. The high degree of plasticity demonstrated by macrophages in pathological conditions can be attributed to a) dynamic regulation of gene expression and b) rapid activation of signaling cascades that determine their effector functions. Signaling cascades triggered by local environmental cues and controlling the transcriptional machinery, ultimately determine the effector functions of macrophages in the tumor microenvironment (TME). Hence, understanding and modulating these ...

show abstract

Paxillin: a crossroad in pathological cell migration

Cited by 272 publications

References 121 publications

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

Loss of Hem1 disrupts macrophage function and impacts on migration, phagocytosis and integrin-mediated adhesion

MicroRNA—A Tumor Trojan Horse for Tumor-Associated Macrophages

Contact Info

Product

Resources

About