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Neuropilin: Handyman and Power Broker in the Tumor Microenvironment

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Book cover Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1223))

Abstract

Neuropilin-1 and neuropilin-2 form a small family of transmembrane receptors, which, due to the lack of a cytosolic protein kinase domain, act primarily as co-receptors for various ligands. Performing at the molecular level both the executive and organizing functions of a handyman as well as of a power broker, they are instrumental in controlling the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. In this setting, the various neuropilin ligands and interaction partners on various cells of the tumor microenvironment, such as cancer cells, endothelial cells, cancer-associated fibroblasts, and immune cells, are surveyed. The suitability of various neuropilin-targeting substances and the intervention in neuropilin-mediated interactions is considered as a possible building block of tumor therapy.

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Abbreviations

3′-UTR:

3′-Untranslated region

ADAM:

A disintegrin and metalloproteinase domain containing protein

ADAMTS:

A disintegrin and metalloproteinase with thrombospondin motifs

AGO:

Argonaute

AKT:

Protein kinase B

ALK:

Anaplastic lymphoma kinase

ALK1:

Activin receptor-like kinase; serine/threonine-protein kinase receptor R3

ALK5:

Activin receptor-like kinase; TGF-β receptor 1

BMP:

Bone morphogenetic protein

BRAF:

Rat/rapidly accelerated fibrosarcoma, isoform B

CAF:

Cancer-associated fibroblasts

CD:

Cluster of differentiation

CendR:

Carboxy-terminal end rule

CSC:

Cancer stem cell

CUB domain:

Cubilin homology domain

DDR:

Discoidin domain receptor

Dlg domain:

Discs large domain

EC:

Endothelial cell

ECM:

Extracellular matrix

EGF(R):

Epidermal growth factor (receptor)

EMT:

Epithelial to mesenchymal transition

EphA2:

Erythropoietin-producing human hepatocellular (EPH) receptor A2

ER:

Endoplasmic reticulum

ErbB:

Erythroblastosis oncogene B

ERK:

Extracellular-signal-regulated kinase

FAK:

Focal adhesion kinase

FGF(R):

Fibroblast growth factor (receptor)

Frzb:

Frizzled-related protein

GAIP:

G alpha interacting protein

GAP:

GTPase activation protein

gC1qR:

Globular head of complement factor C1q binding protein/receptor

GEF:

Guanine nucleotide exchange factor

GIPC:

GAIP interacting protein, C-terminus

GIPC1:

GIPC PDZ domain containing family member 1, synectin

GLI1:

Glioma-associated oncogene homolog 1

GLUT1CBP:

Glucose transporter 1 C-terminal binding protein

Her2:

Human epidermal growth factor receptor 2

HGF(R):

Hepatocyte growth factor (receptor)

HH:

Hedgehog

IGF1R:

Insulin-like growth factor 1 (IGF-1) receptor

IIP1:

Insulin-like growth factor-1 receptor-interacting protein 1

Jnk:

c-Jun N-terminal kinase

KRAS:

Kirsten rat sarcoma

L1CAM:

L1 cell adhesion molecule

LAMC2:

Laminin subunit γ2

lncRNA:

Long noncoding RNA

LRP5:

Low-density lipoprotein receptor related protein 5

MAM domain:

Meprin/A5-protein/PTPmu

MAP(K):

Mitogen-activated protein (kinase)

MET:

Mesenchymal-epithelial transition factor (MET) proto-oncogene

miR:

microRNA

MMP:

Matrix metalloproteinase

NIP:

Neuropilin-1 interacting protein

NRP:

Neuropilin

p130Cas:

CRK-associated substrate

PDGF(R):

Platelet-derived growth factor (receptor)

PDZ:

Postsynaptic density/discs large/zonula occludens-1

PI3K:

Phosphoinositide 3-kinase

PKC:

Protein kinase C

PlGF(R):

Placenta growth factor (receptor)

PSD-95 domain:

Postsynaptic density protein 95 domain

PTEN:

Phosphatase and tensin homolog

PTPmu:

Protein tyrosine phosphatase μ

RAS:

Rat sarcoma

RhoGEF:

Rho guanine nucleotide exchange factor 1

RTK:

Receptor-type tyrosine kinase

SAPK1:

Stress-activated protein kinase 1

SEMA:

Semaphorin

SEMCAP1:

Semaphorin 4C (SEMA4C)-interacting protein 1

SMAD:

sma(ll) and Daf-4 homolog

sNRP:

Soluble neuropilin

Src:

Sarcoma

Syx:

Synectin-binding GEF

TAM:

Tumor-associated macrophage

TEC:

Tumor endothelial cell

TFPI1:

Tissue factor pathway inhibitor

TGF-β(R):

Transforming growth factor-β (receptor)

TIE:

Tyrosine kinase with immunoglobulin-like and EGF-like domains

TIP2:

Tax-interacting protein 2

TORC2:

Rapamycin-sensitive TOR complex 2

Treg:

Regulatory T cell

uPA:

Urokinase plasminogen activator

VCAM-1:

Vascular adhesion protein-1

VEGF(R):

Vascular endothelial growth factor (receptor)

VM:

Vasculogenic mimicry

WIF1:

Wnt inhibitory factor 1

Wnt:

Wingless-related integration site

YAP1:

Yes-associated protein 1

ZO-1 domain:

Zonula occludens-1 domain

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Acknowledgment

The author’s scientific work on NRP1 is financially supported by Deutsche Forschungs gemeinschaft (grant: SFB1009 A09).

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  1. Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany

    Stephan Niland & Johannes A. Eble

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Correspondence to Stephan Niland .

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  1. Columbia University Medical Center, Department of Radiology, New York, NY, USA, Federal University of Minas Gerais, Department of Pathology, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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Niland, S., Eble, J.A. (2020). Neuropilin: Handyman and Power Broker in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1223. Springer, Cham. https://doi.org/10.1007/978-3-030-35582-1_3

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