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1.
Cell ; 182(4): 1044-1061.e18, 2020 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-32795414

RESUMEN

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias/diagnóstico , Animales , Biomarcadores de Tumor/sangre , Línea Celular , Proteínas del Choque Térmico HSC70/metabolismo , Humanos , Aprendizaje Automático , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Neoplasias/metabolismo , Proteoma/análisis , Proteoma/metabolismo , Proteómica/métodos , Sensibilidad y Especificidad , Tetraspanina 29/metabolismo , Proteínas de Unión al GTP rap/metabolismo
2.
EMBO J ; 41(18): e109288, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-36052513

RESUMEN

Intercellular cross talk between cancer cells and stromal and immune cells is essential for tumor progression and metastasis. Extracellular vesicles and particles (EVPs) are a heterogeneous class of secreted messengers that carry bioactive molecules and that have been shown to be crucial for this cell-cell communication. Here, we highlight the multifaceted roles of EVPs in cancer. Functionally, transfer of EVP cargo between cells influences tumor cell growth and invasion, alters immune cell composition and function, and contributes to stromal cell activation. These EVP-mediated changes impact local tumor progression, foster cultivation of pre-metastatic niches at distant organ-specific sites, and mediate systemic effects of cancer. Furthermore, we discuss how exploiting the highly selective enrichment of molecules within EVPs has profound implications for advancing diagnostic and prognostic biomarker development and for improving therapy delivery in cancer patients. Altogether, these investigations into the role of EVPs in cancer have led to discoveries that hold great promise for improving cancer patient care and outcome.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Comunicación Celular , Humanos , Inmunoterapia , Neoplasias/patología , Microambiente Tumoral
3.
Semin Cancer Biol ; 93: 70-82, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37178822

RESUMEN

Primary tumors secrete a variety of factors to turn distant microenvironments into favorable and fertile 'soil' for subsequent metastases. Among these 'seeding' factors that initiate pre-metastatic niche (PMN) formation, tumor-derived extracellular vesicles (EVs) are of particular interest as tumor EVs can direct organotropism depending on their surface integrin profiles. In addition, EVs also contain versatile, bioactive cargo, which include proteins, metabolites, lipids, RNA, and DNA fragments. The cargo incorporated into EVs is collectively shed from cancer cells and cancer-associated stromal cells. Increased understanding of how tumor EVs promote PMN establishment and detection of EVs in bodily fluids highlight how tumor EVs could serve as potential diagnostic and prognostic biomarkers, as well as provide a therapeutic target for metastasis prevention. This review focuses on tumor-derived EVs and how they direct organotropism and subsequently modulate stromal and immune microenvironments at distal sites to facilitate PMN formation. We also outline the progress made thus far towards clinical applications of tumor EVs.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Humanos , Neoplasias/metabolismo , Vesículas Extracelulares/metabolismo , Comunicación Celular , Microambiente Tumoral
4.
Nat Methods ; 16(12): 1269-1273, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31712780

RESUMEN

Extracellular vesicles (EVs) are secreted nanosized particles with many biological functions and pathological associations. The inability to image EVs in fixed tissues has been a major limitation to understanding their role in healthy and diseased tissue microenvironments. Here, we show that crosslinking mammalian tissues with formaldehyde results in significant EV loss, which can be prevented by additional fixation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for visualization of EVs in a range of normal and cancer tissues.


Asunto(s)
Vesículas Extracelulares/ultraestructura , Fijación del Tejido/métodos , Animales , Carbodiimidas , Bovinos , Línea Celular Tumoral , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Cuerpo Vítreo/ultraestructura
5.
J Cell Sci ; 129(20): 3685-3693, 2016 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-27672021

RESUMEN

Autophagy, a pathway for lysosomal-mediated cellular degradation, has recently been described as a regulator of cell migration. Although the molecular mechanisms underlying autophagy-dependent motility are only beginning to emerge, new work demonstrates that selective autophagy mediated by the autophagy cargo receptor, NBR1, specifically promotes the dynamic turnover of integrin-based focal adhesion sites during motility. Here, we discuss the detailed mechanisms through which NBR1-dependent selective autophagy supports focal adhesion remodeling, and we describe the interconnections between this pathway and other established regulators of focal adhesion turnover, such as microtubules. We also highlight studies that examine the contribution of autophagy to selective degradation of proteins that mediate cellular tension and to integrin trafficking; these findings hint at further roles for autophagy in supporting adhesion and migration. Given the recently appreciated importance of selective autophagy in diverse cellular processes, we propose that further investigation into autophagy-mediated focal adhesion turnover will not only shed light onto how focal adhesions are regulated but will also unveil new mechanisms regulating selective autophagy.


Asunto(s)
Autofagia , Movimiento Celular , Animales , Adhesión Celular , Adhesiones Focales/metabolismo , Humanos , Integrinas/metabolismo , Transporte de Proteínas
6.
Bioorg Med Chem Lett ; 25(17): 3495-500, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26142947

RESUMEN

The triazolyl amide γ-secretase modulators are potent alternatives to the cinnamyl amides that have entered the clinic for the treatment of Alzheimer's disease. Herein we build on the lead benzoazepinones described in our prior communication with imidazomethoxyarene moiety alternatives that offer opportunities to fine tune physical properties as well as address hERG binding and PK. Both half-life and bioavailability were significantly improved, especially in dog, with robust brain Aß42 lowering maintained in both transgenic mouse and rat.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/farmacocinética , Animales , Disponibilidad Biológica , Ratones , Ratones Transgénicos , Ratas
7.
Bioorg Med Chem Lett ; 21(13): 4083-7, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21616665

RESUMEN

Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of γ-secretase activity, excellent pharmacokinetics and good central lowering of Aß42 in Sprague-Dawley rats.


Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/metabolismo , Triazoles/síntesis química , Triazoles/farmacología , Péptidos beta-Amiloides/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Unión Proteica , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Triazoles/metabolismo
8.
STAR Protoc ; 2(1): 100225, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33786456

RESUMEN

We developed a modified protocol, based on differential ultracentrifugation (dUC), to isolate extracellular vesicles and particles (specifically exomeres) (EVPs) from various human and murine sources, including cell lines, surgically resected tumors and adjacent tissues, and bodily fluids, such as blood, lymphatic fluid, and bile. The diversity of these samples requires robust and highly reproducible protocols and refined isolation technology, such as asymmetric-flow field-flow fractionation (AF4). Our isolation protocol allows for preparation of EVPs for various downstream applications, including proteomic profiling. For complete details on the use and execution of this protocol, please refer to Hoshino et al. (2020).


Asunto(s)
Líquidos Corporales/química , Centrifugación por Gradiente de Densidad , Vesículas Extracelulares/química , Fraccionamiento de Campo-Flujo , Proteómica , Animales , Línea Celular , Humanos , Ratones
9.
Bioorg Med Chem Lett ; 20(2): 755-8, 2010 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-20005099

RESUMEN

We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Abeta42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects.


Asunto(s)
Acetatos/química , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Flúor/química , Piperidinas/química , Acetatos/síntesis química , Acetatos/farmacocinética , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Compuestos de Diazonio/química , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Piperidinas/síntesis química , Piperidinas/farmacocinética , Ratas , Receptores Notch/metabolismo
10.
Bioorg Med Chem Lett ; 20(7): 2279-82, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20207146

RESUMEN

The development of a novel series of purines as gamma-secretase modulators for potential use in the treatment of Alzheimer's disease is disclosed herein. Optimization of a previously disclosed pyrimidine series afforded a series of potent purine-based gamma-secretase modulators with 300- to 2000-fold in vitro selectivity over inhibition of Notch cleavage and that selectively reduces Alphabeta42 in an APP-YAC transgenic mouse model.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Fragmentos de Péptidos/antagonistas & inhibidores , Purinas/química , Purinas/uso terapéutico , Secretasas de la Proteína Precursora del Amiloide/genética , Péptidos beta-Amiloides/metabolismo , Animales , Humanos , Ratones , Ratones Transgénicos , Fragmentos de Péptidos/metabolismo , Purinas/farmacología , Receptores Notch/metabolismo , Relación Estructura-Actividad
11.
Dev Cell ; 52(5): 591-604.e6, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32084360

RESUMEN

Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation of autophagy strongly attenuates primary mammary tumor growth, impaired autophagy promotes spontaneous metastasis and enables the outgrowth of disseminated tumor cells into overt macro-metastases. Transcriptomic analysis reveals that autophagy deficiency elicits a subpopulation of otherwise luminal tumor cells exhibiting basal differentiation traits, which is reversed upon preventing accumulation of the autophagy cargo receptor, Neighbor to BRCA1 (NBR1). Furthermore, pharmacological and genetic induction of autophagy suppresses pro-metastatic differentiation and metastatic outgrowth. Analysis of human breast cancer data reveal that autophagy gene expression inversely correlates with pro-metastatic differentiation signatures and predicts overall and distant metastasis-free survival. Overall, these findings highlight autophagy-dependent control of NBR1 as a key determinant of metastatic progression.


Asunto(s)
Autofagia , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Animales , Células Cultivadas , Femenino , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Células MCF-7 , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Transcriptoma
12.
Bioorg Med Chem Lett ; 19(4): 1168-72, 2009 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-19138845

RESUMEN

The successful application of both solid and solution phase library synthesis, combined with tight integration into the medicinal chemistry effort, resulted in the efficient optimization of a novel structural series of selective HDAC1/HDAC2 inhibitors by the MRL-Boston Parallel Medicinal Chemistry group. An initial lead from a small parallel library was found to be potent and selective in biochemical assays. Advanced compounds were the culmination of iterative library design and possess excellent biochemical and cellular potency, as well as acceptable PK and efficacy in animal models.


Asunto(s)
Inhibidores de Histona Desacetilasas , Animales , Técnicas Químicas Combinatorias , Perros , Diseño de Fármacos , Histona Desacetilasa 1 , Histona Desacetilasa 2 , Humanos , Estructura Molecular , Ratas , Proteínas Represoras/antagonistas & inhibidores , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Cancer Cell ; 35(1): 3-5, 2019 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-30645974

RESUMEN

Tumor-derived extracellular vesicles promote metastasis by inducing functional changes in cells at pre-metastatic sites conducive for tumor cell colonization. In this issue of Cancer Cell, Ortiz and colleagues show that type I interferon regulates extracellular vesicle uptake and that modulating this pathway holds promise for treating metastasis.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Oxiesteroles , Humanos , Interferones
14.
Dev Cell ; 49(3): 347-360, 2019 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-31063754

RESUMEN

Metastasis, a critical phase of tumor progression, remains a primary challenge in treating cancer and a major cause of cancer mortality. Cell-cell communication via extracellular vesicles (exosomes and microvesicles) between primary tumor cells and the microenvironment of distant organs is crucial for pre-metastatic niche (PMN) formation and metastasis. Here, we review work on the contribution of exosome cargo to cancer progression, the role of exosomes in PMN establishment, and the function of exosomes in organotropic metastasis. We also describe the clinical utility of exosomes.


Asunto(s)
Exosomas/patología , Metástasis de la Neoplasia/patología , Neoplasias/patología , Animales , Comunicación Celular , Progresión de la Enfermedad , Exosomas/metabolismo , Fibroblastos/metabolismo , Humanos , Invasividad Neoplásica/patología , Neoplasias/metabolismo , Neovascularización Patológica/patología , Microambiente Tumoral
15.
Nat Cell Biol ; 21(11): 1403-1412, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31685984

RESUMEN

The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.


Asunto(s)
Neoplasias Encefálicas/genética , Exosomas/metabolismo , Regulación Neoplásica de la Expresión Génica , Hialuronoglucosaminidasa/genética , Neovascularización Patológica/genética , Microambiente Tumoral/genética , Animales , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Quimiocina CCL1/genética , Quimiocina CCL1/metabolismo , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Exosomas/patología , Humanos , Hialuronoglucosaminidasa/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Metástasis de la Neoplasia , Neovascularización Patológica/metabolismo , Neovascularización Patológica/mortalidad , Neovascularización Patológica/patología , Transducción de Señal , Análisis de Supervivencia , Carga Tumoral , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Bioorg Med Chem Lett ; 18(23): 6104-9, 2008 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-18951790

RESUMEN

A potent family of spirocyclic nicotinyl aminobenzamide selective HDAC1/HDAC2 inhibitors (SHI-1:2) is profiled. The incorporation of a biaryl zinc-binding motif into a nicotinyl scaffold resulted in enhanced potency and selectivity versus HDAC3, but also imparted hERG activity. It was discovered that increasing polar surface area about the spirocycle attenuates this liability. Compound 12 induced a 4-fold increase in acetylated histone H2B in an HCT-116 xenograft model study with acute exposure, and inhibited tumor growth in a 21-day efficacy study with qd dosing.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Canales de Potasio Éter-A-Go-Go/metabolismo , Inhibidores de Histona Desacetilasas , Niacinamida/síntesis química , Niacinamida/farmacología , Compuestos de Espiro/síntesis química , Compuestos de Espiro/farmacología , Animales , Antineoplásicos/química , Benzamidas/síntesis química , Benzamidas/química , Benzamidas/farmacología , Técnicas Químicas Combinatorias , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go/efectos de los fármacos , Células HCT116 , Histona Desacetilasas , Histonas/análisis , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Niacinamida/química , Isoformas de Proteínas , Compuestos de Espiro/química , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Bioorg Med Chem Lett ; 18(3): 973-8, 2008 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-18182289

RESUMEN

We report herein the initial exploration of novel selective HDAC1/HDAC2 inhibitors (SHI-1:2). Optimized SHI-1:2 structures exhibit enhanced intrinsic activity against HDAC1 and HDAC2, and are greater than 100-fold selective versus other HDACs, including HDAC3. Based on the SAR of these agents and our current understanding of the HDAC active site, we postulate that the SHI-1:2 extend the existing HDAC inhibitor pharmacophore to include an internal binding domain.


Asunto(s)
Derivados del Benceno/síntesis química , Derivados del Benceno/farmacología , Inhibidores de Histona Desacetilasas , Modelos Moleculares , Derivados del Benceno/química , Sitios de Unión/efectos de los fármacos , Histona Desacetilasa 1 , Histona Desacetilasa 2 , Histona Desacetilasas/química , Histona Desacetilasas/metabolismo , Humanos , Estructura Molecular , Isoformas de Proteínas , Proteínas Represoras , Relación Estructura-Actividad
18.
Nat Cell Biol ; 20(3): 332-343, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29459780

RESUMEN

The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.


Asunto(s)
Fraccionamiento Celular/métodos , Exosomas/metabolismo , Nanopartículas , Neoplasias/metabolismo , Proteínas/metabolismo , Animales , Biomarcadores/metabolismo , ADN/genética , ADN/metabolismo , Metabolismo Energético , Exosomas/clasificación , Exosomas/genética , Exosomas/patología , Femenino , Glicómica , Glicosilación , Células HCT116 , Humanos , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Metabolómica , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Neoplasias/genética , Neoplasias/patología , Células PC-3 , Fenotipo , Proteómica , ARN/genética , ARN/metabolismo , Transducción de Señal , Distribución Tisular
19.
Autophagy ; 12(10): 1958-1959, 2016 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-27484104

RESUMEN

Macroautophagy/autophagy has classically been recognized for its vital role in supporting cellular survival during various stresses. However, emerging work has demonstrated that selective autophagy has an impact on diverse cell biological processes by mediating the degradation of various cellular contents during normal cellular homeostasis. We recently established that selective autophagy supports cell migration by promoting the turnover of integrin-based cell-matrix adhesion sites, or focal adhesions (FAs). The autophagy cargo receptor NBR1 acts as a critical mediator of this pathway by promoting targeting of autophagosomes to FAs, leading to their disassembly via the sequestration of FA proteins. Our results demonstrate FAs as a new cellular target for selective autophagy.


Asunto(s)
Autofagia , Uniones Célula-Matriz/metabolismo , Adhesiones Focales/metabolismo , Proteínas/metabolismo , Animales , Movimiento Celular , Humanos , Modelos Biológicos
20.
Cancer Cell ; 30(2): 189-191, 2016 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-27505667

RESUMEN

Pre-Metastatic Niches (PMNs) result from communications between primary tumors and the microenvironment of future distant metastasis via tumor-derived factors. In this issue of Cancer Cell, Liu et al. show that TLR3 activation in lung epithelial cells by tumor exosomal RNAs triggers neutrophil recruitment, which contributes to PMN formation and metastasis.


Asunto(s)
Neoplasias , Microambiente Tumoral , Células Epiteliales , Humanos , Pulmón , Metástasis de la Neoplasia , ARN Neoplásico
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