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Cell surface–anchored serine proteases in cancer progression and metastasis

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Abstract

Over the last two decades, a novel subgroup of serine proteases, the cell surface–anchored serine proteases, has emerged as an important component of the human degradome, and several members have garnered significant attention for their roles in cancer progression and metastasis. A large body of literature describes that cell surface–anchored serine proteases are deregulated in cancer and that they contribute to both tumor formation and metastasis through diverse molecular mechanisms. The loss of precise regulation of cell surface–anchored serine protease expression and/or catalytic activity may be contributing to the etiology of several cancer types. There is therefore a strong impetus to understand the events that lead to deregulation at the gene and protein levels, how these precipitate in various stages of tumorigenesis, and whether targeting of selected proteases can lead to novel cancer intervention strategies. This review summarizes current knowledge about cell surface–anchored serine proteases and their role in cancer based on biochemical characterization, cell culture–based studies, expression studies, and in vivo experiments. Efforts to develop inhibitors to target cell surface–anchored serine proteases in cancer therapy will also be summarized.

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Abbreviations

ADC :

antibody drug conjugate

ALL :

acute lymphocytic leukemia

AML :

acute myeloid leukemia

APC :

adenomatous polyposis coli

AR :

androgen receptor

ARIH :

autosomal recessive icthyosis with hypotrichosis

BODIPY :

borondipyrromethene

CAF :

cancer-associated fibroblast

CAP1 :

channel-activating protease-1

CLL :

chronic lymphocytic leukemia

CML :

chronic myeloid leukemia

COX-2 :

cyclooxygenase-2

CRC :

colorectal cancer

CT :

computed tomography

DESC :

differentially expressed in squamous cell carcinoma

DMBA :

dimethylbenzanthracene

DHT :

dihydrotestosterone

ECM :

extracellular matrix

ECRG :

esophageal cancer-related gene

EGFR :

epidermal growth factor receptor

EMT :

epithelial to mesenchymal transition

EOC :

epithelial ovarian cancer

ERG :

estrogen-regulated gene

ERK :

extracellular signal-regulated kinase

ESCC :

esophageal squamous cell carcinoma

ETS :

erythroblast transformation specific

FAP :

fibroblast activation protein

GnT-V :

beta1,6-n-acetylglucosaminyltransferase-V

GPI :

glycosyl-phosphatidylinositol

HAI-1 :

hepatocyte growth factor inhibitor-1

HAI-2 :

hepatocyte growth factor inhibitor-2

HAT :

human airway trypsin-like

HGF :

hepatocyte growth factor

HGFA :

hepatocyte growth factor activator

HIF-1a :

hypoxia-inducible factor 1-alpha

HNSCC :

head and neck squamous cell carcinoma

IHC :

immunohistochemistry

IN-1 :

matriptase inhibitor-1

K5 :

keratin-5

K14 :

keratin-14

kbt :

ketobenzothiazole

KD :

knock-down

KD1-PEG :

PEGylated form of the Kunitz domain-1

KO :

knock-out

kt :

ketothiazole

Ln-332 :

laminin-332

LPB :

large probasin

LMP :

low malignant potential

Mab :

monoclonal antibody

MAPK :

mitogen-activated protein kinase

MCL :

mantle cell lymphoma

MCOTI-II :

Momordica cochinchinensis trypsin inhibitor-II

MMAE :

monomethyl auristatin-E

MMP :

matrix metalloprotease

MMTV :

mouse mammary tumor virus

MSP :

macrophage stimulating protein

mTor :

mammalian/mechanistic target of rapamycin

NF :

nuclear factor

NIR :

near-infrared

NPC :

nasopharyngeal carcinoma

NSCLC :

nonsmall cell lung cancer

OSCC :

oral squamous cell carcinoma

PAR-2 :

proteinase-activated receptor-2

PB :

probasin

PCI :

protein C inhibitor

PDAC :

pancreatic ductal adenocarcinoma

PDX :

patient-derived xenograft

PDGF :

platelet-derived growth factor

PDGFR :

platelet-derived growth factor receptor

PEG :

polyethylene glycol

PGE 2 :

prostaglandin E2

PI3K :

Phosphoinositide 3-kinase

PIN :

prostatic intraepithelial neoplasia

PN-1 :

protease nextin-1

PrAg :

protective antigen

PSA :

prostate-specific antigen

PymT :

polyomavirus middle T

RON :

Recepteur d’Origine Nantais

S1p :

sphingosine-1-phosphate

SAM :

S-adenosyl-l-methionine

SAR :

structure–activity relationship

SCC :

squamous cell carcinoma

SCID :

severe combined immunodeficiency

scFv :

single-chain variable fragment

SFTI-1 :

unflower-derived trypsin inhibitor

SNP :

single nucleotide polymorphism

SPECT :

single-photon emission computed tomography

Sphk1 :

sphingosine kinase 1

STAT3 :

signal transducer and activator of transcription 3

Tag :

T antigen

TMPRSS :

transmembrane protease, serine

TNBC :

triple-negative breast cancer

TRAMP :

transgenic adenocarcinoma of the mouse prostate

TTSP :

type II transmembrane serine protease

UPA :

urokinase type plasminogen activator

uPAR :

urokinase-type plasminogen activator receptor

WT :

wild-type

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Funding

This work was supported by NIH/NCI R01CA222359A (KL), Susan G. Komen IBC17511329 (KL) and IBC18511329 (K.L), and an NIH/NCI Training grant (CEM) awarded to Wayne State University Cancer Biology Graduate Program (Ruth L. Kirschstein National Research Service Award T32-CA009531).

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  1. Department of Pharmacology, Wayne State University School of Medicine, Gordon H. Scott Hall of Basic Medical Sciences, Room 6332, 540 East Canfield, Detroit, MI, 48201, USA

    Carly E. Martin & Karin List

  2. Department of Oncology, Wayne State University and Barbara Ann Karmanos Cancer Institute, Gordon H. Scott Hall of Basic Medical Sciences, Room 6332, 540 East Canfield, Detroit, MI, 48201, USA

    Carly E. Martin & Karin List

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  1. Carly E. Martin
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Correspondence to Karin List.

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Martin, C.E., List, K. Cell surface–anchored serine proteases in cancer progression and metastasis. Cancer Metastasis Rev 38, 357–387 (2019). https://doi.org/10.1007/s10555-019-09811-7

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