Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors

Mauro, Concetta Di; Pesapane, Ada; Formisano, Luigi; Rosa, Roberta; Damato, Valentina; Ciciola, Paola; Servetto, Alberto; Marciano, Roberta; Orsini, Roberta Clara; Monteleone, Francesca; Zambrano, Nicola; Fontanini, Gabriella; Servadio, Adele; Pignataro, Giuseppe; Grumetto, Lucia; Lavecchia, Antonio; Bruzzese, Dario; Iaccarino, Antonino; Troncone, Giancarlo; Veneziani, Bianca Maria; Montuori, Nunzia; Placido, Sabino De; Bianco, Roberto

doi:10.1038/s41598-017-10062-1

Cited by 65 publications

(48 citation statements)

References 34 publications

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“…Our research also proved that PLAU expression in lung cancer tissue was signi cantly increased. The complex enzyme can promote the migration and in ltration of tumor cells by destroying the cell matrix [51]. CTSD protein is a kind of cathepsin.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Gong

Wei

et al. 2020

Preprint

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Background: Shenlian Capsule is a Chinese medicine compound approved by the China Food and Drug Administration (CFDA) for the treatment of advanced non-small cell lung cancer(NSCLC). However, due to its complex constituents, cause its effective active compounds and main action mechanisms for treating diseases are still not fully clear. The purpose of this work is to explore the active ingredients and mechanisms of Shenlian Capsule treatment NSCLC through a system pharmacological approach. Methods: First, a database of Shenlian Capsule chemical composition was constructed by retrieving Chinese herbal medicine data. Absorption, distribution, metabolism and excretion (ADME) methods were used to screen potential active compounds. Predict active compound targets with a large-scale molecular network target prediction technology. Clustering of active compounds obtained through cluster analysis by MECODE plug-in, each cluster obtains the main pathways through enrichment analysis method. To get all targets related to survival in NSCLC, the survival related targets were intersected with the compounds target (C-T) network to get the survival related targets for Shenlian Capsule. Finally, a batch molecular docking technique was used to verify the effect of active compounds of Shenlian Capsule on survival-related targets.Results: The Shenlian Capsule C-T network was constructed with 117 potential compounds and 47 targets. Treatment of NSCLC with Shenlian Capsule through enrichment analysis may involve multiple pathways such as anti-inflammatory, immune regulation, regulation of cell cycle, apoptosis, antiviral, cell hypoxia, angiogenesis and so on. Shenlian Capsule has eight survival-related genes in non-small cell lung adenocarcinoma (LUAD) and two survival-related genes in non-small cell squamous cell lung carcinoma (LUSC). It is known through molecular docking that the active compound has lower energy after conformation with survival-related genes, and has lower binding energy and stable binding.Conclusion: In this study, the potential compounds of active compounds in Shenlian Capsule were first predicted using network pharmacology technology. Through the enrichment analysis, the main pathways of the role of Shenlian Capsule were outcropped. Secondly, by combining bioinformatics and network pharmacology, Shenlian Capsule can be regulated to target survival-related targets. Finally, the molecular docking technique shows the relationship between active compounds and survival-related targets after docking. This work provided a scientific basis for the clinical role of Shenlian Capsule in the treatment of NSCLC, provided a research basis for further clarifying the active ingredients and mechanism of Shenlian Capsule in the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Gong

Wei

et al. 2020

Preprint

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“…In addition, an increasing number of proteins involved in the development of several malignant cancers, tumor cell invasion and metastasis are being associated with lipid rafts (290), such as the GPI-anchored cell membrane receptor urokinase-type plasminogen activator receptor (uPAR) (286,291), and the type 1 transmembrane glycoprotein mucin 1 (MUC1) (292, 293), further supporting a major role for lipid rafts in tumor progression. MUC1 is often overexpressed in metastatic cancers and used as a diagnostic marker for metastatic progression (294).…”

Section: Rafts and Metastasismentioning

confidence: 99%

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Mollinedo

Gajate

2020

Journal of Lipid Research

189

206

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Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

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“…The role of KRAS in facilitating tumor metastasis depends on the effect of activated metalloproteases-7 and urokinase plasminogen activator, which breakdown and promote migration through the basement membrane, leading to the dissemination of cancer cells from the primary tumor [ 107 , 108 , 109 ].…”

Section: Krasmentioning

confidence: 99%

Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine

Sammarco

Gallo

Vescio

et al. 2020

JCM

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Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called “ideal biomarkers”, for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.

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Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors

Cited by 65 publications

References 34 publications

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine

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