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


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.


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



antibody drug conjugate


acute lymphocytic leukemia


acute myeloid leukemia


adenomatous polyposis coli


androgen receptor


autosomal recessive icthyosis with hypotrichosis




cancer-associated fibroblast


channel-activating protease-1


chronic lymphocytic leukemia


chronic myeloid leukemia




colorectal cancer


computed tomography


differentially expressed in squamous cell carcinoma






extracellular matrix


esophageal cancer-related gene


epidermal growth factor receptor


epithelial to mesenchymal transition


epithelial ovarian cancer


estrogen-regulated gene


extracellular signal-regulated kinase


esophageal squamous cell carcinoma


erythroblast transformation specific


fibroblast activation protein






hepatocyte growth factor inhibitor-1


hepatocyte growth factor inhibitor-2


human airway trypsin-like


hepatocyte growth factor


hepatocyte growth factor activator


hypoxia-inducible factor 1-alpha


head and neck squamous cell carcinoma




matriptase inhibitor-1










PEGylated form of the Kunitz domain-1








large probasin


low malignant potential


monoclonal antibody


mitogen-activated protein kinase


mantle cell lymphoma


Momordica cochinchinensis trypsin inhibitor-II


monomethyl auristatin-E


matrix metalloprotease


mouse mammary tumor virus


macrophage stimulating protein


mammalian/mechanistic target of rapamycin


nuclear factor




nasopharyngeal carcinoma


nonsmall cell lung cancer


oral squamous cell carcinoma


proteinase-activated receptor-2




protein C inhibitor


pancreatic ductal adenocarcinoma


patient-derived xenograft


platelet-derived growth factor


platelet-derived growth factor receptor


polyethylene glycol


prostaglandin E2


Phosphoinositide 3-kinase


prostatic intraepithelial neoplasia


protease nextin-1


protective antigen


prostate-specific antigen


polyomavirus middle T


Recepteur d’Origine Nantais






structure–activity relationship


squamous cell carcinoma


severe combined immunodeficiency


single-chain variable fragment


unflower-derived trypsin inhibitor


single nucleotide polymorphism


single-photon emission computed tomography


sphingosine kinase 1


signal transducer and activator of transcription 3


T antigen


transmembrane protease, serine


triple-negative breast cancer


transgenic adenocarcinoma of the mouse prostate


type II transmembrane serine protease


urokinase type plasminogen activator


urokinase-type plasminogen activator receptor




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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