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Cancer and Metastasis Reviews

, Volume 38, Issue 3, pp 357–387 | Cite as

Cell surface–anchored serine proteases in cancer progression and metastasis

  • Carly E. Martin
  • Karin ListEmail author
Article

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.

Keywords

Type II transmembrane serine proteases Cancer Matriptase Hepsin TMPRSS2 TMPRSS3 TMPRSS4 Prostasin Testisin 

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

PGE2

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

Notes

Funding information

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacologyWayne State University School of MedicineDetroitUSA
  2. 2.Department of OncologyWayne State University and Barbara Ann Karmanos Cancer InstituteDetroitUSA

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