Maspin

Serpin peptidase inhibitor, clade B (ovalbumin), member 5
PDB rendering based on 1wz9.
Available structures PDB 1WZ9, 1XQG, 1XQJ, 1XU8
Identifiers
Symbols	SERPINB5; PI5; maspin
External IDs	OMIM: 154790 MGI: 109579 HomoloGene: 20580 GeneCards: SERPINB5 Gene
Gene Ontology Molecular function • serine-type endopeptidase inhibitor activity • protein binding Cellular component • extracellular region • extracellular space • cytoplasm Biological process • morphogenesis of an epithelium • cellular component movement • negative regulation of endopeptidase activity • regulation of proteolysis • extracellular matrix organization • regulation of epithelial cell proliferation • prostate gland morphogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5268	20724
Ensembl	ENSG00000206075	ENSMUSG00000067006
UniProt	P36952	P70124
RefSeq (mRNA)	NM_002639.4	NM_009257.3
RefSeq (protein)	NP_002630.2	NP_033283.1
Location (UCSC)	Chr 18: 61.14 – 61.17 Mb	Chr 1: 108.76 – 108.78 Mb
PubMed search	[1]	[2]

Maspin (mammary serine protease inhibitor) also known as serpin B5 is a protein that in humans is encoded by the SERPINB5 gene. This protein belongs to the serpin (serine protease inhibitor) superfamily. SERPINB5 also functions as a tumor suppressor gene in epithelial cells. The expressed protein suppresses the ability of cancer cells to invade and metastasize other tissues. The protein also functions as an angiogenesis inhibitor.

Tissue distribution

Maspin is expressed in the prostate, thymus, testis, intestine, tongue, lung, and the thymus.

Serpin superfamily

Main article: serpin

Maspin is a member of the serpin superfamily of serine protease inhibitors. The primary function of most members of this family is to regulate the break down of proteins by inhibiting the catalytic activity of proteinases. Through this mechanism of action, serpins regulate a number of cellular processes including phagocytosis, coagulation, and fibrinolysis.

Serpins have a complex structure, a key component of which is the reactive site loop, RSL. Inhibitory serpins transition between a stress and relaxed stage. The catalytic serine residue in the protease target attacks the stressed conformation of the RSL loop to form an acyl intermediate. The loop then undergoes a conformational change to the relaxed state irreversibly trapping the protease in an inactive state. Hence the serpine functions as a suicide inhibitor of the protease. This transition does not occur in serpins that lack inhibitory activity.

Function

Though maspin is a part of the serpin superfamily, it's mechanism of action differs somewhat from other members of the family. More specifically, the RSL loop in maspin does not transition between a stressed and relaxed state and is shorter than the RSL loop in other serpins. However this shorter loop is necessary for maspin’s ability to suppress tumors by inhibiting cell invasion and motility. Furthermore, while maspin is an inhibitory serpin, but does not inhibit serine proteinases. Instead, maspin functions as an inhibitor of histone deacetylase 1 (HDAC1).

Tumors require blood in order to proliferate. Tumors invade other cells and begin to spread through a process known as metastasis. Metastasis is one of the key steps in cancer progression that causes cancer-related deaths. Maspin has been shown to inhibit all of these functions. In both prokaryotic and eukaryotic hosts, maspin was able to inhibit the invasion of breast cancer. Normal mRNA expresses maspin, but tumor-derived mammary epithelial cells do not. The consistent down regulation of maspin in breast cancer suggests maspin place a role in tumor suppression. Maspin significantly correlates with tumor differentiation grade or lymph node status, but not with recurrence rates. Maspin reduced the motility of tumor cells by 75 percent within 24 hours.

Maspin treatment of breast cancer cells leads to increased focal adhesions and stress fibers that in turn reduce cell motility. Less motile breast cancer cells were able to “revert to a more epithelial-like phenotype”. When tumor cells are treated with maspin, 53 percent of the tumors stopped growing completely with in a week. Tumor growth returned once the addition of maspin ceased. In addition, maspin able to regulate motility.

Clinical significance

Deficiency in the expression of maspin been associated with increased risks of prostate and breast cancer.

It has also been associated with tumors of the pancreas.

Further reading

• Sager R, Sheng S, Pemberton P, Hendrix MJ (1998). "Maspin. A tumor suppressing serpin.". Adv. Exp. Med. Biol. 425: 77–88. PMID 9433491. 
• Sheng S (2006). "The promise and challenge toward the clinical application of maspin in cancer.". Front. Biosci. 9: 2733–45. doi:10.2741/1432. PMID 15353310. 
• Lockett J, Yin S, Li X, et al. (2006). "Tumor suppressive maspin and epithelial homeostasis.". J. Cell. Biochem. 97 (4): 651–60. doi:10.1002/jcb.20721. PMID 16329135. 
• Chen EI, Yates JR (2006). "Maspin and tumor metastasis.". IUBMB Life 58 (1): 25–9. doi:10.1080/15216540500531721. PMID 16540429. 
• Khalkhali-Ellis Z (2007). "Maspin: the new frontier.". Clin. Cancer Res. 12 (24): 7279–83. doi:10.1158/1078-0432.CCR-06-1589. PMC 3175762. PMID 17189399. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3175762. 
• Schneider SS, Schick C, Fish KE, et al. (1995). "A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.". Proc. Natl. Acad. Sci. U.S.A. 92 (8): 3147–51. doi:10.1073/pnas.92.8.3147. PMC 42122. PMID 7724531. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42122. 
• Pemberton PA, Wong DT, Gibson HL, et al. (1995). "The tumor suppressor maspin does not undergo the stressed to relaxed transition or inhibit trypsin-like serine proteases. Evidence that maspin is not a protease inhibitory serpin.". J. Biol. Chem. 270 (26): 15832–7. doi:10.1074/jbc.270.26.15832. PMID 7797587. 
• Zou Z, Anisowicz A, Hendrix MJ, et al. (1994). "Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.". Science 263 (5146): 526–9. doi:10.1126/science.8290962. PMID 8290962. 
• Pemberton PA, Tipton AR, Pavloff N, et al. (1998). "Maspin is an intracellular serpin that partitions into secretory vesicles and is present at the cell surface.". J. Histochem. Cytochem. 45 (12): 1697–706. PMID 9389773. 
• Xia W, Lau YK, Hu MC, et al. (2000). "High tumoral maspin expression is associated with improved survival of patients with oral squamous cell carcinoma.". Oncogene 19 (20): 2398–403. doi:10.1038/sj.onc.1203535. PMID 10828881. 
• Biliran H, Sheng S (2002). "Pleiotrophic inhibition of pericellular urokinase-type plasminogen activator system by endogenous tumor suppressive maspin.". Cancer Res. 61 (24): 8676–82. PMID 11751384. 
• Blacque OE, Worrall DM (2002). "Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types I and III collagen.". J. Biol. Chem. 277 (13): 10783–8. doi:10.1074/jbc.M110992200. PMID 11788595. 
• Dokras A, Gardner LM, Kirschmann DA, et al. (2002). "The tumour suppressor gene maspin is differentially regulated in cytotrophoblasts during human placental development.". Placenta 23 (4): 274–80. doi:10.1053/plac.2001.0784. PMID 11969337. 
• Jiang N, Meng Y, Zhang S, et al. (2002). "Maspin sensitizes breast carcinoma cells to induced apoptosis.". Oncogene 21 (26): 4089–98. doi:10.1038/sj.onc.1205507. PMID 12037665. 
• Odero-Marah VA, Khalkhali-Ellis Z, Schneider GB, et al. (2002). "Tyrosine phosphorylation of maspin in normal mammary epithelia and breast cancer cells.". Biochem. Biophys. Res. Commun. 295 (4): 800–5. doi:10.1016/S0006-291X(02)00764-7. PMID 12127964. 
• Maass N, Biallek M, Rösel F, et al. (2002). "Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer.". Biochem. Biophys. Res. Commun. 297 (1): 125–8. doi:10.1016/S0006-291X(02)02136-8. PMID 12220518. 
• Sood AK, Fletcher MS, Gruman LM, et al. (2002). "The paradoxical expression of maspin in ovarian carcinoma.". Clin. Cancer Res. 8 (9): 2924–32. PMID 12231537. 
• Son HJ, Sohn TS, Song SY, et al. (2003). "Maspin expression in human gastric adenocarcinoma.". Pathol. Int. 52 (8): 508–13. doi:10.1046/j.1440-1827.2002.01381.x. PMID 12366809. 
• Bass R, Fernández AM, Ellis V (2003). "Maspin inhibits cell migration in the absence of protease inhibitory activity.". J. Biol. Chem. 277 (49): 46845–8. doi:10.1074/jbc.C200532200. PMID 12384513. 

External links

• The MEROPS online database for peptidases and their inhibitors: I04.980
• MeSH maspin