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Gene Review

Mtss1  -  metastasis suppressor 1

Mus musculus

Synonyms: 2310003N14Rik, BC024131, D130001D01Rik, MIM, Metastasis suppressor protein 1, ...
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Disease relevance of Mtss1

  • Missing in metastasis (MIM) gene encodes an actin binding protein that is expressed at low levels in a subset of malignant cell lines [1].
  • Spondylocostal dysostosis (SD, MIM 277300) is a group of vertebral malsegmentation syndromes with reduced stature resulting from axial skeletal defects [2].
  • Keutel syndrome (KS, MIM 245150) is an autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis and midfacial hypoplasia [3].
  • Clustered attacks of epileptic episodes originating from the frontal lobe during sleep are the main symptoms of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE, MIM 600513) [4].
  • Hirschsprung disease (HSCR, MIM #142623) is a multigenic neurocristopathy (neural crest disorder) characterized by absence of enteric ganglia in a variable portion of the distal colon [5].

Psychiatry related information on Mtss1


High impact information on Mtss1


Chemical compound and disease context of Mtss1

  • We postulate that MIM-B may be a regulator of actin assembly downstream of tyrosine kinase signalling and that this activity may explain the involvement of MIM in the metastasis of cancer cells [11].

Biological context of Mtss1

  • However, an MIM mutant with deletion of the WH2 domain, which is responsible for G-actin binding, enhanced cell motility [1].
  • These data show that MIM is an ATP-G-actin binding protein that regulates cytoskeletal dynamics in specialized mammalian cell-types [12].
  • This mouse gene also shows strong sequence homology to human MIM (Missing in Metastasis), a cDNA fragment that is present in non-metastatic but absent in metastatic bladder cancer cell lines [12].
  • They further suggest that a melanoma metastasis-suppressor gene(s) is encoded on chromosome 6 or is regulated by genes on chromosome 6 [13].
  • To study the molecular and cellular basis of mosaicism, we established a mouse model for the autosomal-dominant skin blistering disorder, epidermolytic hyperkeratosis (MIM 113800), which is caused by mutations in either keratin K1 or K10 [14].

Anatomical context of Mtss1


Associations of Mtss1 with chemical compounds


Regulatory relationships of Mtss1


Other interactions of Mtss1

  • We previously identified Basal cell carcinoma-enriched gene 4 (BEG4)/Missing in Metastasis (MIM), a Shh-inducible, Wiskott-Aldrich homology 2 domain-containing protein that potentiates Gli transcription (Callahan, C.A., T. Ofstad, L. Horng, J.K. Wang, H.H. Zhen, P.A. Coulombe, and A.E. Oro. 2004. Genes Dev. 18:2724-2729) [15].
  • DRnm23 belongs to a multigene family which includes nm23-H1, the first bona fide metastasis suppressor gene, nm23-H2, nm23-H4, and nm23-H5 [20].
  • Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect [21].
  • The nm23-M1, a putative metastasis-suppressor gene, and its homologs are involved in development and differentiation [22].

Analytical, diagnostic and therapeutic context of Mtss1

  • Site-directed mutagenesis demonstrates that the actin monomer-binding site resides in the C-terminal WH2 domain of MIM [12].
  • A PCR analysis of various microcell hybrid clones with sequence-tagged site markers indicates that the metastasis suppressor activity is located in the q24.2 region of chromosome 16 [23].
  • Intrasplenic transplantation of GFP-expressing parental MIM cells into Fas-injured livers of SCID mice revealed liver-reconstituting activity [24].
  • The use of these models has enabled preclinical chemotherapeutic, chemoprevention, and genetic therapy studies in vivo, the testing of gene delivery systems, and the identification of tumour and metastasis suppressor and inducer genes [25].
  • CONCLUSIONS: Animal models of metastasis have supported drug development and have been useful for identification of metastasis suppressor and promoter genes as novel targets for the development of novel therapies [26].


  1. Differential regulation of cortactin and N-WASP-mediated actin polymerization by missing in metastasis (MIM) protein. Lin, J., Liu, J., Wang, Y., Zhu, J., Zhou, K., Smith, N., Zhan, X. Oncogene (2005) [Pubmed]
  2. Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Bulman, M.P., Kusumi, K., Frayling, T.M., McKeown, C., Garrett, C., Lander, E.S., Krumlauf, R., Hattersley, A.T., Ellard, S., Turnpenny, P.D. Nat. Genet. (2000) [Pubmed]
  3. Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Munroe, P.B., Olgunturk, R.O., Fryns, J.P., Van Maldergem, L., Ziereisen, F., Yuksel, B., Gardiner, R.M., Chung, E. Nat. Genet. (1999) [Pubmed]
  4. The nicotinic receptor beta 2 subunit is mutant in nocturnal frontal lobe epilepsy. De Fusco, M., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., Ballabio, A., Wanke, E., Casari, G. Nat. Genet. (2000) [Pubmed]
  5. Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Southard-Smith, E.M., Kos, L., Pavan, W.J. Nat. Genet. (1998) [Pubmed]
  6. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Indo, Y., Tsuruta, M., Hayashida, Y., Karim, M.A., Ohta, K., Kawano, T., Mitsubuchi, H., Tonoki, H., Awaya, Y., Matsuda, I. Nat. Genet. (1996) [Pubmed]
  7. Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism. Avela, K., Lipsanen-Nyman, M., Idänheimo, N., Seemanová, E., Rosengren, S., Mäkelä, T.P., Perheentupa, J., Chapelle, A.D., Lehesjoki, A.E. Nat. Genet. (2000) [Pubmed]
  8. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Frattini, A., Orchard, P.J., Sobacchi, C., Giliani, S., Abinun, M., Mattsson, J.P., Keeling, D.J., Andersson, A.K., Wallbrandt, P., Zecca, L., Notarangelo, L.D., Vezzoni, P., Villa, A. Nat. Genet. (2000) [Pubmed]
  9. KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Dong, J.T., Lamb, P.W., Rinker-Schaeffer, C.W., Vukanovic, J., Ichikawa, T., Isaacs, J.T., Barrett, J.C. Science (1995) [Pubmed]
  10. MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription. Callahan, C.A., Ofstad, T., Horng, L., Wang, J.K., Zhen, H.H., Coulombe, P.A., Oro, A.E. Genes Dev. (2004) [Pubmed]
  11. MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. Woodings, J.A., Sharp, S.J., Machesky, L.M. Biochem. J. (2003) [Pubmed]
  12. Mouse MIM, a tissue-specific regulator of cytoskeletal dynamics, interacts with ATP-actin monomers through its C-terminal WH2 domain. Mattila, P.K., Salminen, M., Yamashiro, T., Lappalainen, P. J. Biol. Chem. (2003) [Pubmed]
  13. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Lee, J.H., Miele, M.E., Hicks, D.J., Phillips, K.K., Trent, J.M., Weissman, B.E., Welch, D.R. J. Natl. Cancer Inst. (1996) [Pubmed]
  14. Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders. Arin, M.J., Longley, M.A., Wang, X.J., Roop, D.R. J. Cell Biol. (2001) [Pubmed]
  15. Receptor tyrosine phosphatase-dependent cytoskeletal remodeling by the hedgehog-responsive gene MIM/BEG4. Gonzalez-Quevedo, R., Shoffer, M., Horng, L., Oro, A.E. J. Cell Biol. (2005) [Pubmed]
  16. Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency. Schmidt, A., Marescau, B., Boehm, E.A., Renema, W.K., Peco, R., Das, A., Steinfeld, R., Chan, S., Wallis, J., Davidoff, M., Ullrich, K., Waldschütz, R., Heerschap, A., De Deyn, P.P., Neubauer, S., Isbrandt, D. Hum. Mol. Genet. (2004) [Pubmed]
  17. Increased sensitivity to cisplatin by nm23-transfected tumor cell lines. Ferguson, A.W., Flatow, U., MacDonald, N.J., Larminat, F., Bohr, V.A., Steeg, P.S. Cancer Res. (1996) [Pubmed]
  18. Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Seraj, M.J., Samant, R.S., Verderame, M.F., Welch, D.R. Cancer Res. (2000) [Pubmed]
  19. Involvement of histone deacetylation in ras-induced down-regulation of the metastasis suppressor RECK. Chang, H.C., Liu, L.T., Hung, W.C. Cell. Signal. (2004) [Pubmed]
  20. The nucleoside diphosphate kinase activity of DRnm23 is not required for inhibition of differentiation and induction of apoptosis in 32Dcl3 myeloid precursor cells. Venturelli, D., Cesi, V., Ransac, S., Engelhard, A., Perrotti, D., Calabretta, B. Exp. Cell Res. (2000) [Pubmed]
  21. Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect. Fujita, H., Okada, F., Hamada , J., Hosokawa, M., Moriuchi, T., Koya, R.C., Kuzumaki, N. Int. J. Cancer (2001) [Pubmed]
  22. Identification of novel mRNA transcripts of the nm23-M1 gene that are modulated during mouse embryo development and are differently expressed in adult murine tissues. Gervasi, F., Capozza, F., Bruno, T., Fanciulli, M., Lombardi, D. DNA Cell Biol. (1998) [Pubmed]
  23. Human chromosome 16 suppresses metastasis but not tumorigenesis in rat prostatic tumor cells. Mashimo, T., Watabe, M., Cuthbert, A.P., Newbold, R.F., Rinker-Schaeffer, C.W., Helfer, E., Watabe, K. Cancer Res. (1998) [Pubmed]
  24. Immortalized p19ARF null hepatocytes restore liver injury and generate hepatic progenitors after transplantation. Mikula, M., Fuchs, E., Huber, H., Beug, H., Schulte-Hermann, R., Mikulits, W. Hepatology (2004) [Pubmed]
  25. From genetic abnormality to metastases: murine models of breast cancer and their use in the development of anticancer therapies. Ottewell, P.D., Coleman, R.E., Holen, I. Breast Cancer Res. Treat. (2006) [Pubmed]
  26. Animal models of bone metastasis. Rosol, T.J., Tannehill-Gregg, S.H., LeRoy, B.E., Mandl, S., Contag, C.H. Cancer (2003) [Pubmed]
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