Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA

  • Authors:
    • Tania Fontanil
    • Yamina Mohamedi
    • Manuel M. Esteban
    • Alvaro J. Obaya
    • Santiago Cal
  • View Affiliations

  • Published online on: April 23, 2014     https://doi.org/10.3892/or.2014.3146
  • Pages: 2792-2796
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Abstract

Polyserase-1/TMPRSS9 is a type II transmembrane serine protease showing a complex molecular architecture characterized by the presence of three tandem serine protease domains in its amino acid sequence. This protease is widely expressed in mouse and human tissues, however, its functional significance is unknown in both normal and pathological conditions. In the present study, we evaluated the possible role of polyserase-1 in cancer progression. First, we showed that polyserase-1 increased the invasive capacities of PANC-1 and SK-PC-3 pancreatic cancer cells. Moreover, the presence of polyserase-1 enhanced anchorage-independent growth and diminished the adhesion capability of PANC-1 cells to different extracellular matrix components. These effects were mediated by the efficient conversion of pro-uPA to active uPA and high phosphorylation levels of ERK detected in the PANC-1 cells expressing exogenous polyserase-1. Collectively, our data suggest that polyserase-1 may be involved in cancer progression and, similarly to what has been proposed for the closely related serine proteases matriptase and TMPRSS4, inhibition of TMPRSS9 activity may contribute to the inhibition of tumor growth.

References

1 

Hornebeck W, Emonard H, Monboisse JC and Bellon G: Matrix-directed regulation of pericellular proteolysis and tumor progression. Semin Cancer Biol. 12:231–241. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Wilkins-Port CE, Higgins SP, Higgins CE, Kobori-Hotchkiss I and Higgins PJ: Complex regulation of the pericellular proteolytic microenvironment during tumor progression and wound repair: functional interactions between the serine rrotease and matrix metalloproteinase cascades. Biochem Res Int. 2012:4543682012.

3 

Netzel-Arnett S, Hooper JD, Szabo R, et al: Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev. 22:237–258. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Lu D, Yuan X, Zheng X and Sadler JE: Bovine proenteropeptidase is activated by trypsin, and the specificity of enteropeptidase depends on the heavy chain. J Biol Chem. 272:31293–31300. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Gladysheva IP, Wang D, McNamee RA, et al: Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy. Hypertension. 61:327–332. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Folgueras AR, de Lara FM, Pendas AM, et al: Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood. 112:2539–2545. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Guipponi M, Tan J, Cannon PZ, et al: Mice deficient for the type II transmembrane serine protease, TMPRSS1/hepsin, exhibit profound hearing loss. Am J Pathol. 171:608–616. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Wu Q: Type II transmembrane serine proteases. Curr Top Dev Biol. 54:167–206. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Webb SL, Sanders AJ, Mason MD and Jiang WG: Type II transmembrane serine protease (TTSP) deregulation in cancer. Front Biosci. 16:539–552. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Hashimoto T, Kato M, Shimomura T and Kitamura N: TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor. FEBS J. 277:4888–4900. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Wu Q and Parry G: Hepsin and prostate cancer. Front Biosci. 12:5052–5059. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Chen CH, Su KY, Tao MH, et al: Decreased expressions of hepsin in human hepatocellular carcinomas. Liver Int. 26:774–780. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Szabo R and Bugge TH: Type II transmembrane serine proteases in development and disease. Int J Biochem Cell Biol. 40:1297–1316. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Kosa P, Szabo R, Molinolo AA and Bugge TH: Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis. Oncogene. 31:3679–3695. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Lang JC and Schuller DE: Differential expression of a novel serine protease homologue in squamous cell carcinoma of the head and neck. Br J Cancer. 84:237–243. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Viloria CG, Peinado JR, Astudillo A, et al: Human DESC1 serine protease confers tumorigenic properties to MDCK cells and it is upregulated in tumours of different origin. Br J Cancer. 97:201–209. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Cal S, Quesada V, Garabaya C and Lopez-Otin C: Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product. Proc Natl Acad Sci USA. 100:9185–9190. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Okumura Y, Hayama M, Takahashi E, et al: Serase-1B, a new splice variant of polyserase-1/TMPRSS9, activates urokinase-type plasminogen activator and the proteolytic activation is negatively regulated by glycosaminoglycans. Biochem J. 400:551–561. 2006. View Article : Google Scholar

19 

Cantero D, Friess H, Deflorin J, et al: Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer. 75:388–395. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Wallrapp C, Hahnel S, Muller-Pillasch F, et al: A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 60:2602–2606. 2000.PubMed/NCBI

21 

Uhland K, Siphos B, Arkona C, et al: Use of IHC and newly designed matriptase inhibitors to elucidate the role of matriptase in pancreatic ductal adenocarcinoma. Int J Oncol. 35:347–357. 2009.PubMed/NCBI

22 

Kilpatrick LM, Harris RL, Owen KA, et al: Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase. Blood. 108:2616–2623. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Min HJ, Lee Y, Zhao XF, et al: TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion. Cell Signal. 26:398–408. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Deer EL, Gonzalez-Hernandez J, Coursen JD, et al: Phenotype and genotype of pancreatic cancer cell lines. Pancreas. 39:425–435. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Vila MR, Lloreta J, Schussler MH, Berrozpe G, Welt S and Real FX: New pancreas cancers cell lines that represent distinct stages of ductal differentiation. Lab Invest. 72:395–404. 1995.PubMed/NCBI

26 

Noel A, Gutierrez-Fernandez A, Sounni NE, et al: New and paradoxical roles of matrix metalloproteinases in the tumor microenvironment. Front Pharmacol. 3:1402012. View Article : Google Scholar : PubMed/NCBI

27 

Ochi N, Tanasanvimon S, Matsuo Y, et al: Protein kinase D1 promotes anchorage-independent growth, invasion, and angiogenesis by human pancreatic cancer cells. J Cell Physiol. 226:1074–1081. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Guo XZ, Xu JH, Liu MP, et al: KAI1 inhibits anchorage-dependent and -independent pancreatic cancer cell growth. Oncol Rep. 14:59–63. 2005.PubMed/NCBI

29 

Suzuki M, Kobayashi H, Kanayama N, et al: Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J Biol Chem. 279:14899–14908. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Liu J, Ben QW, Yao WY, et al: BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK. Front Biosci. 17:2541–2549. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Touab M, Villena J, Barranco C, Arumi-Uria M and Bassols A: Versican is differentially expressed in human melanoma and may play a role in tumor development. Am J Pathol. 160:549–557. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Welman A, Sproul D, Mullen P, et al: Diversity of matriptase expression level and function in breast cancer. PLoS One. 7:e341822012. View Article : Google Scholar : PubMed/NCBI

33 

Jung H, Lee KP, Park SJ, et al: TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition. Oncogene. 27:2635–2647. 2008. View Article : Google Scholar

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June 2014
Volume 31 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
APA
Fontanil, T., Mohamedi, Y., Esteban, M.M., Obaya, A.J., & Cal, S. (2014). Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA. Oncology Reports, 31, 2792-2796. https://doi.org/10.3892/or.2014.3146
MLA
Fontanil, T., Mohamedi, Y., Esteban, M. M., Obaya, A. J., Cal, S."Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA". Oncology Reports 31.6 (2014): 2792-2796.
Chicago
Fontanil, T., Mohamedi, Y., Esteban, M. M., Obaya, A. J., Cal, S."Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA". Oncology Reports 31, no. 6 (2014): 2792-2796. https://doi.org/10.3892/or.2014.3146