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Gene Review

KLK6  -  kallikrein-related peptidase 6

Homo sapiens

Synonyms: Bssp, Kallikrein-6, Klk7, Neurosin, PRSS18, ...
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Disease relevance of KLK6

  • PATIENTS AND METHODS: Using real-time reverse transcription-PCR, we analyzed the KLK6 expression status with respect to various clinicopathologic variables in 66 patients with gastric cancer [1].
  • Elevated KLK6 expression was significantly correlated with serosal invasion (P < 0.05), liver metastasis (P < 0.05), and advanced Duke's stage (P < 0.01) [2].
  • Twelve kallikreins, including KLK6, are concurrently upregulated in ovarian cancer [3].
  • X-profiler comparison of two pools of normal and cancerous pancreatic libraries further verified the significant increase of KLK6 expression levels in pancreatic cancer [4].
  • Similar results were obtained by EST screening; no KLK6 clones were detected in any of the 28 normal libraries examined, while 10 KLK6 EST clones were found in colon adenocarcinoma [4].

Psychiatry related information on KLK6


High impact information on KLK6


Chemical compound and disease context of KLK6

  • We conclude that KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction.British Journal of Cancer (2007) 96, 362-372. doi:10.1038/sj.bjc.6603556 [3].
  • KLK6 can be reactivated in non-expressing breast cancer cells by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), a compound causing DNA demethylation [9].
  • In some breast cancer cell lines, KLK6 expression could be restored by the vitamin D3 analog EB1089 [9].
  • Hybrid sandwich assays (capture antibody for hK6 and detection antibody for inhibitors), utilizing a panel of known serine protease inhibitors, indicated that alpha(1)-antichymotrypsin forms a complex with hK6 in milk and ascites fluid [10].
  • To investigate the role of protease M/neurosin during experimental demyelination and remyelination, mice were fed cuprizone (bis-cyclohexanon oxaldihydrazone) [11].

Biological context of KLK6


Anatomical context of KLK6


Associations of KLK6 with chemical compounds

  • BACKGROUND: The human kallikrein 6 gene (KLK6) encodes for a secreted serine protease, hK6, which is highly expressed in brain [15].
  • Zyme is regulated by steroid hormones in the breast carcinoma cell line BT-474 [13].
  • The screening of fluorescence resonance energy transfer (FRET) peptide families derived from Abz-KLRSSKQ-EDDnp resulted in the finding that Abz-AFRFSQ-EDDnp (where Abz is ortho-aminobenzoic acid and EDDnp is N-[2,4-dinitrophenyl]ethylenediamine)) is the best synthetic substrate described so far for hK6 (kcat/Km 38,667 s(-1) mm(-1)) [8].
  • This report also suggested the possible modulation of ionotropic glutamate receptors and activation of PAR 2 by hK6 [8].
  • However, combined 5-aza-dC/TSA treatment resulted in synergistic activation of KLK6 [9].

Regulatory relationships of KLK6

  • When Zyme cDNA is co-expressed with the APP cDNA in 293 (human embryonic kidney) cells, amyloidogenic fragments are detected using C-terminal antibody to APP [16].

Other interactions of KLK6


Analytical, diagnostic and therapeutic context of KLK6


  1. Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer. Nagahara, H., Mimori, K., Utsunomiya, T., Barnard, G.F., Ohira, M., Hirakawa, K., Mori, M. Clin. Cancer Res. (2005) [Pubmed]
  2. Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. Ogawa, K., Utsunomiya, T., Mimori, K., Tanaka, F., Inoue, H., Nagahara, H., Murayama, S., Mori, M. Clin. Cancer Res. (2005) [Pubmed]
  3. Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects. Shan, S.J., Scorilas, A., Katsaros, D., Diamandis, E.P. Br. J. Cancer (2007) [Pubmed]
  4. In-silico analysis of kallikrein gene expression in pancreatic and colon cancers. Yousef, G.M., Borgoño, C.A., Popalis, C., Yacoub, G.M., Polymeris, M.E., Soosaipillai, A., Diamandis, E.P. Anticancer Res. (2004) [Pubmed]
  5. Decreased cerebrospinal fluid levels of neurosin (KLK6), an aging-related protease, as a possible new risk factor for Alzheimer's disease. Mitsui, S., Okui, A., Uemura, H., Mizuno, T., Yamada, T., Yamamura, Y., Yamaguchi, N. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  6. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. Diamandis, E.P., Scorilas, A., Fracchioli, S., Van Gramberen, M., De Bruijn, H., Henrik, A., Soosaipillai, A., Grass, L., Yousef, G.M., Stenman, U.H., Massobrio, M., Van Der Zee, A.G., Vergote, I., Katsaros, D. J. Clin. Oncol. (2003) [Pubmed]
  7. Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences. Debela, M., Magdolen, V., Schechter, N., Valachova, M., Lottspeich, F., Craik, C.S., Choe, Y., Bode, W., Goettig, P. J. Biol. Chem. (2006) [Pubmed]
  8. Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects. Angelo, P.F., Lima, A.R., Alves, F.M., Blaber, S.I., Scarisbrick, I.A., Blaber, M., Juliano, L., Juliano, M.A. J. Biol. Chem. (2006) [Pubmed]
  9. Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer. Pampalakis, G., Sotiropoulou, G. Biol. Chem. (2006) [Pubmed]
  10. Purification of human kallikrein 6 from biological fluids and identification of its complex with alpha(1)-antichymotrypsin. Hutchinson, S., Luo, L.Y., Yousef, G.M., Soosaipillai, A., Diamandis, E.P. Clin. Chem. (2003) [Pubmed]
  11. Implications of protease M/neurosin in myelination during experimental demyelination and remyelination. Bando, Y., Ito, S., Nagai, Y., Terayama, R., Kishibe, M., Jiang, Y.P., Mitrovic, B., Takahashi, T., Yoshida, S. Neurosci. Lett. (2006) [Pubmed]
  12. Cloning and characterization of novel isoforms of the human kallikrein 6 gene. Pampalakis, G., Kurlender, L., Diamandis, E.P., Sotiropoulou, G. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  13. Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease. Yousef, G.M., Luo, L.Y., Scherer, S.W., Sotiropoulou, G., Diamandis, E.P. Genomics (1999) [Pubmed]
  14. Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases. Komatsu, N., Saijoh, K., Toyama, T., Ohka, R., Otsuki, N., Hussack, G., Takehara, K., Diamandis, E.P. Br. J. Dermatol. (2005) [Pubmed]
  15. Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer's disease patients. Zarghooni, M., Soosaipillai, A., Grass, L., Scorilas, A., Mirazimi, N., Diamandis, E.P. Clin. Biochem. (2002) [Pubmed]
  16. Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain. Little, S.P., Dixon, E.P., Norris, F., Buckley, W., Becker, G.W., Johnson, M., Dobbins, J.R., Wyrick, T., Miller, J.R., MacKellar, W., Hepburn, D., Corvalan, J., McClure, D., Liu, X., Stephenson, D., Clemens, J., Johnstone, E.M. J. Biol. Chem. (1997) [Pubmed]
  17. Role of kallikrein enzymes in the central nervous system. Yousef, G.M., Kishi, T., Diamandis, E.P. Clin. Chim. Acta (2003) [Pubmed]
  18. Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications. Diamandis, E.P., Yousef, G.M., Soosaipillai, A.R., Grass, L., Porter, A., Little, S., Sotiropoulou, G. Clin. Biochem. (2000) [Pubmed]
  19. Kallikreins as markers of disseminated tumour cells in ovarian cancer - a pilot study. Oikonomopoulou, K., Scorilas, A., Michael, I.P., Grass, L., Soosaipillai, A., Rosen, B., Murphy, J., Diamandis, E.P. Tumour Biol. (2006) [Pubmed]
  20. Human kallikrein 6: a new potential serum biomarker for uterine serous papillary cancer. Santin, A.D., Diamandis, E.P., Bellone, S., Soosaipillai, A., Cane, S., Palmieri, M., Burnett, A., Roman, J.J., Pecorelli, S. Clin. Cancer Res. (2005) [Pubmed]
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