Engulfment of particles by phagocytes is induced by their interaction with specific receptors on ... more Engulfment of particles by phagocytes is induced by their interaction with specific receptors on the cell surface, which leads to actin polymerization and the extension of membrane protrusions to form a closed phagosome. Membrane delivery from internal pools is considered to play an important role in pseudopod extension during phagocytosis. Here, we report that endogenous ADP ribosylation factor 6 (ARF6), a small GTP-binding protein, undergoes a sharp and transient activation in macrophages when phagocytosis was initiated via receptors for the Fc portion of immunoglobulins (FcRs). A dominant-negative mutant of ARF6 (T27N mutation) dramatically affected FcR-mediated phagocytosis. Expression of ARF6-T27N lead to a reduction in the focal delivery of vesicle-associated membrane protein 3+ endosomal recycling membranes at phagocytosis sites, whereas actin polymerization was unimpaired. This resulted in an early blockade in pseudopod extension and accumulation of intracellular vesicles, a...
While mutations leading to a fragile envelope of the cell nucleus are well known to cause disease... more While mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to the presence of chronic DNA damage and activation of the ATM kinase. In addition, we found that depletion of the cytoplasmic exonuclease TREX1 is sufficient to abolish the DNA damage in mechanically challenged nuclei and to suppress the phenotypes associated with the loss of nuclear envelope integrity. Our ...
Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells and ... more Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells and neutrophils to internalize, degrade and eventually present peptides derived from particulate antigens. This process relies on profound rearrangements of the actin cytoskeleton and the plasma membrane to engulf particles. Recent work has highlighted the early recruitment of internal membranes derived from endocytic compartments and from the endoplasmic reticulum to allow plasma membrane extension at the onset of phagocytosis. This ensures that the phagosome is rapidly provided with the machinery appropriate for later phagocytic functions, including particle degradation and antigen presentation.
Tumor cells exposed to a physiological matrix of type I collagen fibers form elongated collagenol... more Tumor cells exposed to a physiological matrix of type I collagen fibers form elongated collagenolytic invadopodia, which differ from dotty-like invadopodia forming on the gelatin substratum model. The related scaffold proteins, TKS5 and TKS4, are key components of the mechanism of invadopodia assembly. The molecular events through which TKS proteins direct collagenolytic invadopodia formation are poorly defined. Using coimmunoprecipitation experiments, identification of bound proteins by mass spectrometry, and in vitro pull-down experiments, we found an interaction between TKS5 and FGD1, a guanine nucleotide exchange factor for the Rho-GTPase CDC42, which is known for its role in the assembly of invadopodial actin core structure. A novel cell polarity network is uncovered comprising TKS5, FGD1, and CDC42, directing invadopodia formation and the polarization of MT1-MMP recycling compartments, required for invadopodia activity and invasion in a 3D collagen matrix. Additionally, our da...
Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within... more Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within highly organized epithelium is still unknown. Here, we found that the overexpression of the protein kinase atypical protein kinase C ι (aPKCi), an oncogene, triggers basally oriented epithelial cell extrusion in vivo as a potential mechanism for early breast tumor cell invasion. We found that cell segregation is the first step required for basal extrusion of luminal cells and identify aPKCi and vinculin as regulators of cell segregation. We propose that asymmetric vinculin levels at the junction between normal and aPKCi+ cells trigger an increase in tension at these cell junctions. Moreover, we show that aPKCi+ cells acquire promigratory features, including increased vinculin levels and vinculin dynamics at the cell–substratum contacts. Overall, this study shows that a balance between cell contractility and cell–cell adhesion is crucial for promoting basally oriented cell extrusion, a m...
Annual review of cell and developmental biology, Oct 8, 2016
Metastasis is responsible for most cancer-associated deaths. Accumulating evidence based on 3D mi... more Metastasis is responsible for most cancer-associated deaths. Accumulating evidence based on 3D migration models has revealed a diversity of invasive migratory schemes reflecting the plasticity of tumor cells to switch between proteolytic and nonproteolytic modes of invasion. Yet, initial stages of localized regional tumor dissemination require proteolytic remodeling of the extracellular matrix to overcome tissue barriers. Recent data indicate that surface-exposed membrane type 1-matrix metalloproteinase (MT1-MMP), belonging to a group of membrane-anchored MMPs, plays a central role in pericellular matrix degradation during basement membrane and interstitial tissue transmigration programs. In addition, a large body of work indicates that MT1-MMP is targeted to specialized actin-rich cell protrusions termed invadopodia, which are responsible for matrix degradation. This review describes the multistep assembly of actin-based invadopodia in molecular details. Mechanisms underlying MT1-M...
The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this p... more The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this process are poorly understood. Through a functional siRNA screening of human RAB GTPases, we found that RAB2A, a protein essential for ER-to-Golgi transport, is critical in promoting proteolytic activity and 3D invasiveness of breast cancer (BC) cell lines. Remarkably, RAB2A is amplified and elevated in human BC and is a powerful and independent predictor of disease recurrence in BC patients. Mechanistically, RAB2A acts at two independent trafficking steps. Firstly, by interacting with VPS39, a key component of the late endosomal HOPS complex, it controls post-endocytic trafficking of membrane-bound MT1-MMP, an essential metalloprotease for matrix remodeling and invasion. Secondly, it further regulates Golgi transport of E-cadherin, ultimately controlling junctional stability, cell compaction, and tumor invasiveness. Thus, RAB2A is a novel trafficking determinant essential for regulation ...
During their metastatic spread, cancer cells need to remodel the extracellular matrix in order to... more During their metastatic spread, cancer cells need to remodel the extracellular matrix in order to migrate through stromal compartments adjacent to the primary tumor. Dissemination of breast carcinoma cells is mediated by membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14), the main invadopodial matrix degradative component. Here, we identify MT1-MMP as a novel interacting partner of dual-specificity LIM Kinase-1 and -2 (LIMK1/2), and provide several evidence for phosphorylation of tyrosine Y573 in the cytoplasmic domain of MT1-MMP by LIMK. Phosphorylation of Y573 influences association of F-actin binding protein cortactin to MT1-MMP-positive endosomes and invadopodia formation and matrix degradation. Moreover, we show that LIMK1 regulates cortactin association to MT1-MMP-positive endosomes, while LIMK2 controls invadopodia-associated cortactin. In turn, LIMK1 and LIMK2 are required for MT1-MMP-dependent matrix degradation and cell invasion in a three-dimensional type I collagen...
Alterations of chromatin modifiers are frequent in cancer, but their functional consequences ofte... more Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study ...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Understanding breast tumor ... more Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Understanding breast tumor progression requires insights both at the molecular and cellular levels. In particular, the transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is a key, yet poorly understood event. Membrane-Type 1 matrix metalloproteinase (MT1-MMP) is critical for pericellular remodelling of the basement membrane and interstitial collagen during invasion by carcinoma cells. The role of MT1-MMP during the transition from DCIS to IDC was investigated using an intraductal human-in-mouse xenograft model. Breast tumor-derived MCF10.DCIS.com cells, which express MT1-MMP were injected into the primary mammary ducts of female SCID mice. Histological analysis revealed a progression from DCIS, to microinvasive and invasive lesions by 5, 7-8 and 10-12 weeks post-injection, respectively. Immunohistochemistry (IHC) staining showed homogeneous expression of MT1-MMP over the tumor section at DCIS stage, and up-regulation at the edge of the tumours at microinvasive and invasive states. In microinvasives lesion, up-regulation of MT1-MMP in tumour cells coincided with disruption of the basement membrane. At later stages, one characteristic of invasive lesions is the increase in collagen fibers deposition. Interestingly, MT1-MMP expression was also increased at the front of infiltrating tumours in contact with the stroma. After 10 weeks, intraductally injected cells knocked down for MT1-MMP developed invasive tumours only in 20% of injected mammary glands, while 100% of glands injected with control cells developed infiltrating lesions. All together, these results demonstrated that MT1-MMP is instrumental for the transition from in situ to invasive breast tumours. IHC staining revealed a strong correlation of the expression of the basal marker p63 and MT1-MMP in tumour cells both at the microinvasive and invasive stages. One hypothesis was that contact of tumor cells with the stroma triggered induction of p63 that in turn up-regulated MT1-MMP. Along this line, we found that MCF10.DCIS.com cells plated on type I collagen up-regulated p63 and MT1-MMP, both at the mRNA and protein levels, while silencing of p63 abolished collagen-dependent MT1-MMP increase. At the functional level, silencing of MT1-MMP or p63 inhibited invasion of multicellular spheroids into 3D type collagen as well as the cells capacity to degrade collagen I fibers. Finally, MT1-MMP expression was analysed by IHC staining on human tissue microarray comprising 432 IDCs, 40 microinfiltrated lesions and 68 DCIS. MT1-MMP was upregulated in IDC as compared to DCIS. Invasive triple-negative breast (TNBC) and grade III tumours expressed highest MT1-MMP levels. To our knowledge, this is the first demonstration that up-regulation of MT1-MMP is associated with invasiveness, histopathologic grade and molecular subtypes in human breast cancer. We also observed 10% of TNBC expressing p63 and found a positive correlation with MT1-MMP expression suggesting an interplay between p63 and MT1-MMP during progression. Citation Format: Catalina Lodillinsky, Elvira Infante, Laetitia Fuhrmann, Alan Guichard, Joanna Cyrta, Emilie Lagoutte, Marie Irondelle, Sophie Vacher, Ivan Bieche, Marina Glukhova, Anne Vincent-Salomon, Philippe Chavrier. Membrane-anchored MT1-MMP downstream of p63 is essential for the transition of in situ to invasive breast carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-30. doi:10.1158/1538-7445.AM2014-LB-30
Phagocytosis is the uptake of large particles by cells by a mechanism that is based on local rear... more Phagocytosis is the uptake of large particles by cells by a mechanism that is based on local rearrangement of the actin microfilament cytoskeleton. In higher organisms, phagocytic cells are essential for host defence against invading pathogens, and phagocytosis contributes to inflammation and the immune response. In addition, engulfment, defined as the phagocytic clearance of cell corpses generated by programmed cell death or apoptosis, has an essential role in tissue homeostasis. Although morphologically distinct phagocytic events can be observed depending on the type of surface receptor engaged, work over the past two years has revealed the essential underlying role of Rho family proteins and their downstream effectors in controlling actin dynamics during phagocytosis.
Engulfment of particles by phagocytes is induced by their interaction with specific receptors on ... more Engulfment of particles by phagocytes is induced by their interaction with specific receptors on the cell surface, which leads to actin polymerization and the extension of membrane protrusions to form a closed phagosome. Membrane delivery from internal pools is considered to play an important role in pseudopod extension during phagocytosis. Here, we report that endogenous ADP ribosylation factor 6 (ARF6), a small GTP-binding protein, undergoes a sharp and transient activation in macrophages when phagocytosis was initiated via receptors for the Fc portion of immunoglobulins (FcRs). A dominant-negative mutant of ARF6 (T27N mutation) dramatically affected FcR-mediated phagocytosis. Expression of ARF6-T27N lead to a reduction in the focal delivery of vesicle-associated membrane protein 3+ endosomal recycling membranes at phagocytosis sites, whereas actin polymerization was unimpaired. This resulted in an early blockade in pseudopod extension and accumulation of intracellular vesicles, a...
While mutations leading to a fragile envelope of the cell nucleus are well known to cause disease... more While mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to the presence of chronic DNA damage and activation of the ATM kinase. In addition, we found that depletion of the cytoplasmic exonuclease TREX1 is sufficient to abolish the DNA damage in mechanically challenged nuclei and to suppress the phenotypes associated with the loss of nuclear envelope integrity. Our ...
Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells and ... more Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells and neutrophils to internalize, degrade and eventually present peptides derived from particulate antigens. This process relies on profound rearrangements of the actin cytoskeleton and the plasma membrane to engulf particles. Recent work has highlighted the early recruitment of internal membranes derived from endocytic compartments and from the endoplasmic reticulum to allow plasma membrane extension at the onset of phagocytosis. This ensures that the phagosome is rapidly provided with the machinery appropriate for later phagocytic functions, including particle degradation and antigen presentation.
Tumor cells exposed to a physiological matrix of type I collagen fibers form elongated collagenol... more Tumor cells exposed to a physiological matrix of type I collagen fibers form elongated collagenolytic invadopodia, which differ from dotty-like invadopodia forming on the gelatin substratum model. The related scaffold proteins, TKS5 and TKS4, are key components of the mechanism of invadopodia assembly. The molecular events through which TKS proteins direct collagenolytic invadopodia formation are poorly defined. Using coimmunoprecipitation experiments, identification of bound proteins by mass spectrometry, and in vitro pull-down experiments, we found an interaction between TKS5 and FGD1, a guanine nucleotide exchange factor for the Rho-GTPase CDC42, which is known for its role in the assembly of invadopodial actin core structure. A novel cell polarity network is uncovered comprising TKS5, FGD1, and CDC42, directing invadopodia formation and the polarization of MT1-MMP recycling compartments, required for invadopodia activity and invasion in a 3D collagen matrix. Additionally, our da...
Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within... more Metastasis is the main cause of cancer-related deaths. How a single oncogenic cell evolves within highly organized epithelium is still unknown. Here, we found that the overexpression of the protein kinase atypical protein kinase C ι (aPKCi), an oncogene, triggers basally oriented epithelial cell extrusion in vivo as a potential mechanism for early breast tumor cell invasion. We found that cell segregation is the first step required for basal extrusion of luminal cells and identify aPKCi and vinculin as regulators of cell segregation. We propose that asymmetric vinculin levels at the junction between normal and aPKCi+ cells trigger an increase in tension at these cell junctions. Moreover, we show that aPKCi+ cells acquire promigratory features, including increased vinculin levels and vinculin dynamics at the cell–substratum contacts. Overall, this study shows that a balance between cell contractility and cell–cell adhesion is crucial for promoting basally oriented cell extrusion, a m...
Annual review of cell and developmental biology, Oct 8, 2016
Metastasis is responsible for most cancer-associated deaths. Accumulating evidence based on 3D mi... more Metastasis is responsible for most cancer-associated deaths. Accumulating evidence based on 3D migration models has revealed a diversity of invasive migratory schemes reflecting the plasticity of tumor cells to switch between proteolytic and nonproteolytic modes of invasion. Yet, initial stages of localized regional tumor dissemination require proteolytic remodeling of the extracellular matrix to overcome tissue barriers. Recent data indicate that surface-exposed membrane type 1-matrix metalloproteinase (MT1-MMP), belonging to a group of membrane-anchored MMPs, plays a central role in pericellular matrix degradation during basement membrane and interstitial tissue transmigration programs. In addition, a large body of work indicates that MT1-MMP is targeted to specialized actin-rich cell protrusions termed invadopodia, which are responsible for matrix degradation. This review describes the multistep assembly of actin-based invadopodia in molecular details. Mechanisms underlying MT1-M...
The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this p... more The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this process are poorly understood. Through a functional siRNA screening of human RAB GTPases, we found that RAB2A, a protein essential for ER-to-Golgi transport, is critical in promoting proteolytic activity and 3D invasiveness of breast cancer (BC) cell lines. Remarkably, RAB2A is amplified and elevated in human BC and is a powerful and independent predictor of disease recurrence in BC patients. Mechanistically, RAB2A acts at two independent trafficking steps. Firstly, by interacting with VPS39, a key component of the late endosomal HOPS complex, it controls post-endocytic trafficking of membrane-bound MT1-MMP, an essential metalloprotease for matrix remodeling and invasion. Secondly, it further regulates Golgi transport of E-cadherin, ultimately controlling junctional stability, cell compaction, and tumor invasiveness. Thus, RAB2A is a novel trafficking determinant essential for regulation ...
During their metastatic spread, cancer cells need to remodel the extracellular matrix in order to... more During their metastatic spread, cancer cells need to remodel the extracellular matrix in order to migrate through stromal compartments adjacent to the primary tumor. Dissemination of breast carcinoma cells is mediated by membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14), the main invadopodial matrix degradative component. Here, we identify MT1-MMP as a novel interacting partner of dual-specificity LIM Kinase-1 and -2 (LIMK1/2), and provide several evidence for phosphorylation of tyrosine Y573 in the cytoplasmic domain of MT1-MMP by LIMK. Phosphorylation of Y573 influences association of F-actin binding protein cortactin to MT1-MMP-positive endosomes and invadopodia formation and matrix degradation. Moreover, we show that LIMK1 regulates cortactin association to MT1-MMP-positive endosomes, while LIMK2 controls invadopodia-associated cortactin. In turn, LIMK1 and LIMK2 are required for MT1-MMP-dependent matrix degradation and cell invasion in a three-dimensional type I collagen...
Alterations of chromatin modifiers are frequent in cancer, but their functional consequences ofte... more Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study ...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Understanding breast tumor ... more Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Understanding breast tumor progression requires insights both at the molecular and cellular levels. In particular, the transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is a key, yet poorly understood event. Membrane-Type 1 matrix metalloproteinase (MT1-MMP) is critical for pericellular remodelling of the basement membrane and interstitial collagen during invasion by carcinoma cells. The role of MT1-MMP during the transition from DCIS to IDC was investigated using an intraductal human-in-mouse xenograft model. Breast tumor-derived MCF10.DCIS.com cells, which express MT1-MMP were injected into the primary mammary ducts of female SCID mice. Histological analysis revealed a progression from DCIS, to microinvasive and invasive lesions by 5, 7-8 and 10-12 weeks post-injection, respectively. Immunohistochemistry (IHC) staining showed homogeneous expression of MT1-MMP over the tumor section at DCIS stage, and up-regulation at the edge of the tumours at microinvasive and invasive states. In microinvasives lesion, up-regulation of MT1-MMP in tumour cells coincided with disruption of the basement membrane. At later stages, one characteristic of invasive lesions is the increase in collagen fibers deposition. Interestingly, MT1-MMP expression was also increased at the front of infiltrating tumours in contact with the stroma. After 10 weeks, intraductally injected cells knocked down for MT1-MMP developed invasive tumours only in 20% of injected mammary glands, while 100% of glands injected with control cells developed infiltrating lesions. All together, these results demonstrated that MT1-MMP is instrumental for the transition from in situ to invasive breast tumours. IHC staining revealed a strong correlation of the expression of the basal marker p63 and MT1-MMP in tumour cells both at the microinvasive and invasive stages. One hypothesis was that contact of tumor cells with the stroma triggered induction of p63 that in turn up-regulated MT1-MMP. Along this line, we found that MCF10.DCIS.com cells plated on type I collagen up-regulated p63 and MT1-MMP, both at the mRNA and protein levels, while silencing of p63 abolished collagen-dependent MT1-MMP increase. At the functional level, silencing of MT1-MMP or p63 inhibited invasion of multicellular spheroids into 3D type collagen as well as the cells capacity to degrade collagen I fibers. Finally, MT1-MMP expression was analysed by IHC staining on human tissue microarray comprising 432 IDCs, 40 microinfiltrated lesions and 68 DCIS. MT1-MMP was upregulated in IDC as compared to DCIS. Invasive triple-negative breast (TNBC) and grade III tumours expressed highest MT1-MMP levels. To our knowledge, this is the first demonstration that up-regulation of MT1-MMP is associated with invasiveness, histopathologic grade and molecular subtypes in human breast cancer. We also observed 10% of TNBC expressing p63 and found a positive correlation with MT1-MMP expression suggesting an interplay between p63 and MT1-MMP during progression. Citation Format: Catalina Lodillinsky, Elvira Infante, Laetitia Fuhrmann, Alan Guichard, Joanna Cyrta, Emilie Lagoutte, Marie Irondelle, Sophie Vacher, Ivan Bieche, Marina Glukhova, Anne Vincent-Salomon, Philippe Chavrier. Membrane-anchored MT1-MMP downstream of p63 is essential for the transition of in situ to invasive breast carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-30. doi:10.1158/1538-7445.AM2014-LB-30
Phagocytosis is the uptake of large particles by cells by a mechanism that is based on local rear... more Phagocytosis is the uptake of large particles by cells by a mechanism that is based on local rearrangement of the actin microfilament cytoskeleton. In higher organisms, phagocytic cells are essential for host defence against invading pathogens, and phagocytosis contributes to inflammation and the immune response. In addition, engulfment, defined as the phagocytic clearance of cell corpses generated by programmed cell death or apoptosis, has an essential role in tissue homeostasis. Although morphologically distinct phagocytic events can be observed depending on the type of surface receptor engaged, work over the past two years has revealed the essential underlying role of Rho family proteins and their downstream effectors in controlling actin dynamics during phagocytosis.
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Papers by Philippe Chavrier