The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?

Sanders, Andrew; Webb, Siobhan; Parr, Christian; Mason, Malcolm David; Jiang, Wen Guo

doi:10.2174/1871520611009010064

Cited by 17 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, there is also evidence to suggest that, as with other members of the TTSPs, MT-2 may have a role in cancer development and progression. 84 Although the evidence currently available points to a role for MT-2 only in prostate and breast tumor development, the link between MT-2 and liver tumor is a challenging avenue to explore, especially considering the well-known relationship between iron overload and hepatocellular carcinoma. …”

Section: Resultsmentioning

confidence: 99%

Iron refractory iron deficiency anemia

et al. 2013

View full text Add to dashboard Cite

Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach

show abstract

Section: Resultsmentioning

confidence: 99%

Iron refractory iron deficiency anemia

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The role of extracellular proteolysis in cancer progression has been a subject of investigation for many years especially focusing on secreted proteases, including matrix metalloproteases, cathepsins, and components of the plasminogen activation system. More recently, studies assessing the role of membrane tethered serine proteases in carcinogenesis have emerged, including members of the type II transmembrane serine protease family such as matriptase and matriptase‐2 as well as the GPI‐anchored proteases prostasin and testisin (Hooper et al, 2000; Tang et al, 2005; Chen et al, 2007; List et al, 2009; Sanders et al, 2010). To this end, we now have performed a comprehensive study of the expression of matriptase and its downstream target prostasin in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Strong expression association between matriptase and its substrate prostasin in breast cancer

Bergum

Zoratti

Boerner

et al. 2012

Journal Cellular Physiology

View full text Add to dashboard Cite

Breast cancer tumorigenesis is accompanied by increased levels of extracellular proteases that are capable of remodeling the extracellular matrix as well as cleaving and activating growth factors and signaling receptors that are critically involved in neoplastic progression. Multiple studies implicate the membrane anchored serine protease matriptase (also known as MT-SP1 and epithin) in breast cancer. The pro-form of the GPI-anchored serine protease prostasin has recently been identified as a physiological substrate of matriptase and the two proteases are co-expressed in multiple healthy tissues. In this study, the inter-relationship between the two membrane-anchored serine proteases in breast cancer was investigated using breast cancer cell lines and breast cancer patient samples to delineate the association between matriptase and prostasin. We used Western blotting to determine the expression of matriptase and prostasin proteins in a panel of breast cancer cell lines and immunohistochemistry to assess the expression in serial sections from breast cancer tissue arrays. We demonstrate that the expression of matriptase and prostasin is closely correlated in breast cancer cell lines as well as in breast cancer tissue samples. Furthermore, matriptase and prostasin display a near identical spatial expression pattern in the epithelial compartment of breast cancer tissue. These data suggest that the matriptase-prostasin cascade might play a critical role in breast cancer.

show abstract

“…Once the catalytic domain is released, it migrates as a single or dimeric species (Silvestri et al, 2008). Matriptase-2 shares high structural and enzymatic similarities with matriptase-1, which contains four LDLR repeats instead of three (Sanders et al, 2010), is expressed in epithelial cells, and has been implicated in the progression of cancers, such as breast, prostate, and colorectal cancer (Oberst et al, 2001; Velasco et al, 2002; Kang et al, 2003; Riddick et al, 2005). …”

Section: Biochemistry Of Matriptase-2mentioning

confidence: 99%

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

2014

View full text Add to dashboard Cite

Matriptase-2, encoded by the TMPRSS6 gene, is a member of the type II transmembrane serine protease family. Matriptase-2 has structural and enzymatic similarities to matriptase-1, which has been implicated in cancer progression. Matriptase-2 was later established to be essential in iron homeostasis based on the phenotypes of iron-refractory iron deficiency anemia identified in mouse models as well as in human patients with TMPRSS6 mutations. TMPRSS6 is expressed mainly in the liver and negatively regulates the production of hepcidin, the systemic iron regulatory hormone. This review focuses on the current understanding of matriptase-2 biochemistry, and its role in iron metabolism and cancer progression. In light of recent investigations, the function of matriptase-2 in hepcidin regulation, how it is being regulated, as well as the therapeutic potential of matriptase-2 are also discussed.

show abstract

The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?

Cited by 17 publications

References 0 publications

Iron refractory iron deficiency anemia

Iron refractory iron deficiency anemia

Strong expression association between matriptase and its substrate prostasin in breast cancer

The role of TMPRSS6/matriptase-2 in iron regulation and anemia

Contact Info

Product

Resources

About