The fibrinolytic factor tPA drives LRP1‐mediated melanoma growth and metastasis

Salama, Yousef; Lin, Shiou-Yuh; Dhahri, Douaa; Hattori, Koichi; Heissig, Beate

doi:10.1096/fj.201801339rrr

Cited by 21 publications

(28 citation statements)

References 48 publications

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“…Proteolytic cleavage of LRP-1 results in alpha subunit ligand-binding domain at the N-terminus and ß subunit consisting of other remaining domain at the C-terminus ( Lillis et al, 2008 ). LRP-1 binds to more than 30 ligands, such as ApoE ( Hussain et al, 1999 ), tPA ( Salama et al, 2019 ), a receptor-associated protein (RAP) ( Prasad et al, 2016 ), in addition to trypsin-activated α2-macroglobulin (α2M ∗ ), lactoferrin, Factor VIII and others (for a complete list of ligands, see Herz and Strickland, 2001 ). The presence of different motifs at the cytoplasmic tail of LRP-1, such as two dileucine motifs, NPXY motifs, one YXXL motif has been suggested to be responsible for its high endocytic uptake ( Li et al, 2000 ; Deane et al, 2008 ).…”

Section: Recently Established Nomenclature For Scavenger Receptorsmentioning

confidence: 99%

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

2020

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Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells lining the sinusoidal capillaries of the hepatic system. LSECs are characterized with numerous fenestrae and lack basement membrane as well as a diaphragm. These unique morphological characteristics of LSECs makes them the most permeable endothelial cells of the mammalian vasculature and aid in regulating flow of macromolecules and small lipid-based structures between sinusoidal blood and parenchymal cells. LSECs have a very high endocytic capacity aided by scavenger receptors (SR), such as SR-A, SR-B (SR-B1 and CD-36), SR-E (Lox-1 and mannose receptors), and SR-H (Stabilins). Other high-affinity receptors for mediating endocytosis include the FcγRIIb, which assist in the antibody-mediated removal of immune complexes. Complemented with intense lysosomal activity, LSECs play a vital role in the uptake and degradation of many blood borne waste macromolecules and small (<280 nm) colloids. Currently, seven Toll-like receptors have been investigated in LSECs, which are involved in the recognition and clearance of pathogen-associated molecular pattern (PAMPs) as well as damage associated molecular pattern (DAMP). Along with other SRs, LSECs play an essential role in maintaining lipid homeostasis with the lowdensity lipoprotein receptor-related protein-1 (LRP-1), in juxtaposition with hepatocytes. LSECs co-express two surface lectins called L-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin Receptor (L-SIGN) and liver sinusoidal endothelial cell lectin (LSECtin). LSECs also express several adhesion molecules which are involved in the recruitment of leukocytes at the site of inflammation. Here, we review these cell surface receptors as well as other components expressed by LSECs and their functions in the maintenance of liver homeostasis. We further discuss receptor expression and activity and dysregulation associated with the initiation and progression of many liver diseases, such as hepatocellular carcinoma, liver fibrosis, and cirrhosis, alcoholic and non-alcoholic fatty liver diseases and pseudocapillarization with aging.

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Section: Recently Established Nomenclature For Scavenger Receptorsmentioning

confidence: 99%

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

2020

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“…Although it is well documented that LRP-1 may activate crucial downstream signaling pathways such as Ras, c-Myc, MAPK, and Akt/PI3K, which are widely known as oncogenic pathways, especially in cell proliferation and survival processes (Van Gool et al, 2015), very few data have previously involved LRP-1 during cancer cell proliferation steps. Salama and collaborators reported the involvement of LRP-1:tPA pathway in promoting melanoma cell migration and proliferation (Salama et al, 2019). Their results, using loss-and gain-of-function strategy demonstrated a model wherein LRP-1 drives melanoma growth and metastases by enhancing ERK activation resulting in increased proteolytic events and in changing the cellular content within the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding tumor growth and metastasis, the molecular contribution of LRP-1 remains misunderstood and be highly dependent of the tumor microenvironment. Although LRP-1 expression and its role in cancer hallmarks are now well referenced in glioma (Boyé et al, 2017), melanoma (Salama et al, 2019), thyroid (Perrot et al, 2012;Appert-Collin et al, 2017;Theret et al, 2017), and breast carcinoma (Beaujouin et al, 2010;Tian et al, 2019), little is known about LRP-1 functionalities in colorectal carcinoma (CRC). LRP-1B, a member of LDL-R family highly homologous to LRP-1, is downregulated in the colon cancer tissues and inhibits the growth, migration and metastasis of colon cancer cells (Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

LRP-1 Promotes Colon Cancer Cell Proliferation in 3D Collagen Matrices by Mediating DDR1 Endocytosis

Bennasroune

Collin

et al. 2020

Front. Cell Dev. Biol.

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Low density lipoprotein receptor related protein-1 (LRP-1) is a large ubiquitous endocytic receptor mediating the clearance of various molecules from the extracellular matrix. Several studies have shown that LRP-1 plays crucial roles during tumorigenesis functioning as a main signal pathway regulator, especially by interacting with other cell-surface receptors. Discoïdin Domain Receptors (DDRs), type I collagen receptors with tyrosine kinase activity, have previously been associated with tumor invasion and aggressiveness in diverse tumor environments. Here, we addressed whether it could exist functional interplays between LRP-1 and DDR1 to control colon carcinoma cell behavior in three-dimensional (3D) collagen matrices. We found that LRP-1 established tight molecular connections with DDR1 at the plasma membrane in colon cancer cells. In this tumor context, we provide evidence that LRP-1 regulates by endocytosis the cell surface levels of DDR1 expression. The LRP-1 mediated endocytosis of DDR1 increased cell proliferation by promoting cell cycle progression into S phase and decreasing apoptosis. In this study, we identified a new molecular way that controls the cellsurface expression of DDR1 and consequently the colon carcinoma cell proliferation and apoptosis and highlighted an additional mechanism by which LRP-1 carries out its sensor activity of the tumor microenvironment.

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“…LRP1 s role might vary from one tumor type to another. LRP1 expression levels are often deregulated and reported to be related with advanced tumor stage and poor prognoses in several cancers, such as CRC [46], lung adenocarcinoma [105], melanoma [47], and hepatocellular carcinoma [106]. On the other hand, high LRP1 expression was reported in the advanced tumor stage of astrocytoma [107], endometrial [108], and breast cancer [109], further suggesting conflicting roles of this gene, which warrant future research.…”

Section: Lrp1 Mutationsmentioning

confidence: 99%

“…LRP1 together with its ligands, tissue plasminogen activator (tPA), regulate melanoma growth and lung metastasis in vivo [47].…”

Section: Retrospective Cohortsmentioning

confidence: 99%

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

et al. 2020

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Global statistics have placed colorectal cancer (CRC) as the third most frequently diagnosed cancer and the fourth principal cause of cancer-related deaths worldwide. Improving survival for CRC is as important as early detection. Personalized medicine is important in maximizing an individual’s treatment success and minimizing the risk of adverse reactions. Approaches in achieving personalized therapy in CRC have included analyses of specific genes with its clinical implications. Tumour genotyping via next-generation sequencing has become a standard practice to guide clinicians into predicting tumor behaviour, disease prognosis, and treatment response. Nevertheless, better prognostic markers are necessary to further stratify patients for personalized treatment plans. The discovery of new markers remains indispensable in providing the most effective chemotherapy in order to improve the outcomes of treatment and survival in CRC patients. This review aims to compile and discuss newly discovered, less frequently mutated genes in CRC. We also discuss how these mutations are being used to assist therapeutic decisions and their potential prospective clinical utilities. In addition, we will summarize the importance of profiling the large genomic rearrangements, gene amplification, and large deletions and how these alterations may assist in determining the best treatment option for CRC patients.

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The fibrinolytic factor tPA drives LRP1‐mediated melanoma growth and metastasis

Cited by 21 publications

References 48 publications

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

LRP-1 Promotes Colon Cancer Cell Proliferation in 3D Collagen Matrices by Mediating DDR1 Endocytosis

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

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