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Gene Review

FAT1  -  FAT atypical cadherin 1

Homo sapiens

Synonyms: CDHF7, CDHR8, Cadherin family member 7, Cadherin-related tumor suppressor homolog, FAT, ...


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Disease relevance of FAT

  • FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors [1].
  • FAT1 is over expressed in pre-BALL and potential prognostic marker [2]
  • FAT1 provides a novel minimal residual disease marker in acute lymphoblastic leukaemia  [3]
  • FAT1 is over expressed in Melanoma and undergoes incomplete cleavage [4]
  • Grade 3 DCIS displayed the highest hFAT intensity compared with lower grade tumours, with significant differences between grade 1 and 3 (p = 0.015) and grade 2 and 3 (p = 0.047) [5].
  • METHODS: A total of 326 cases of invasive and in situ breast cancer representing a broad spectrum of histological subtypes were immunostained with affinity-purified rabbit antibodies produced to the cytoplasmic region of hFAT using a standard avidin-biotin system [5]

High impact information on FAT

  • In an epithelial cell wound model, FAT1 knockdown decreased recruitment of endogenous VASP to the leading edge and resulted in impairment of lamellipodial dynamics, failure of polarization, and an attenuation of cell migration [6].
  • In another step, the cleavage product was released to the cytosol and was also found in a low speed pellet fraction, in accordance with the nuclear localization of the cytoplasmic domain of hFat1 [7].
  • Fatty acid bing protein 4 (FABP4) plays a key role in fat regulation in mammals and is a strong positional candidate gene for the FAT1 quantitative trait locus located on porcine chromosome 4 [8].
  • To both improve the comparative map of the entire SSC4 and to define the specific human chromosome region with conserved synteny to FAT1, we have now mapped 103 loci to pig Chromosome 4 using a combination of radiation hybrid and linkage mapping [9].
  • Furthermore, a haplotype analysis suggests that there is genetic heterogeneity at the FAT1 locus within the Landrace breed [10].
  • The FAT1 protein once translated undergoes furin  mediated S1 cleavage forming a non-covalent heterodimer  before achieving cell surface expression although this processing is often perturbed in cancer cells which express non-cleaved FAT1 on the cell surface [4]
  • FAT1 cadherin is multiply phosphorylated  on its ectodomain  but phosphorylation is not catalysed by FJX1  . [11]
  • The ectodomain of FAT1 can also be shed from the cell surface by the sheddase ADAM10, with release of this ectodomain a possible new biomarker  in pancreatic cancer  [12]
  • FAT1 was shown to regulate Hippo   kinase components with loss of FAT1 leading to nucleocytoplasmic relocation of TAZ  and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signaling  [13]

Biological context of FAT


Analytical, diagnostic and therapeutic context of FAT

  • With the sample sizes used in the present study we cannot with great confidence determine whether these smaller effects in some sires are due to chance deviations, epistatic interactions or whether FAT1 is composed of two or more QTLs, each one with a smaller phenotypic effect [14].


  1. Comparative integromics on FAT1, FAT2, FAT3 and FAT4. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  2. The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia. de Bock, C.E., Ardjmand, A., Molloy, T.J., Bone, S.M., Johnstone, D., Campbell, D.M., Shipman, K.L., Yeadon, T.M., Holst, J., Spanevello, M.D., Nelmes, G., Catchpoole, D.R., Lincz, L.F., Boyd, A.W., Burns, G.F., Thorne, R.F. Leukemia. (2012) [Pubmed]
  3. Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia. Ardjmand, A., de Bock, C.E., Shahrokhi, S., Lincz, L.F., Boyd, A.W., Burns, G.F., Thorne, R.F. Hematology. (2013) [Pubmed]
  4. Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products. Sadeqzadeh, E., de Bock, C.E., Zhang, X.D., Shipman, K.L., Scott, N.M., Song, C., Yeadon, T., Oliveira, C.S., Jin, B., Hersey, P., Boyd, A.W., Burns, G.F., Thorne, R.F. J. Biol. Chem. (2011) [Pubmed]
  5. Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis? Kwaepila, N., Burns, G., Leong, A.S. Pathology. (2006) [Pubmed]
  6. Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization. Moeller, M.J., Soofi, A., Braun, G.S., Li, X., Watzl, C., Kriz, W., Holzman, L.B. EMBO J. (2004) [Pubmed]
  7. Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus. Magg, T., Schreiner, D., Solis, G.P., Bade, E.G., Hofer, H.W. Exp. Cell Res. (2005) [Pubmed]
  8. Unexpected High Polymorphism at the FABP4 Gene Unveils a Complex History for Pig Populations. Ojeda, A., Rozas, J., Folch, J.M., P??rez-Enciso, M. Genetics (2006) [Pubmed]
  9. High-resolution comparative mapping of pig Chromosome 4, emphasizing the FAT1 region. Moller, M., Berg, F., Riquet, J., Pomp, D., Archibald, A., Anderson, S., Feve, K., Zhang, Y., Rothschild, M., Milan, D., Andersson, L., Tuggle, C.K. Mamm. Genome (2004) [Pubmed]
  10. Adipocyte fatty-acid binding protein is closely associated to the porcine FAT1 locus on chromosome 4. Mercad??, A., P??rez-Enciso, M., Varona, L., Alves, E., Noguera, J.L., S??nchez, A., Folch, J.M. J. Anim. Sci. (2006) [Pubmed]
  11. FAT1 cadherin is multiply phosphorylated on its ectodomain but phosphorylation is not catalysed by the four-jointed homologue. Sadeqzadeh, E., de Bock, C.E., O'Donnell, M.R., Timofeeva, A., Burns, G.F., Thorne, R.F. FEBS. Lett. (2014) [Pubmed]
  12. A soluble form of the giant cadherin Fat1 is released from pancreatic cancer cells by ADAM10 mediated ectodomain shedding. Wojtalewicz, N., Sadeqzadeh, E., Weiß, J.V., Tehrani, M.M., Klein-Scory, S., Hahn, S., Schmiegel, W., Warnken, U., Schnölzer, M., de Bock, C.E., Thorne, R.F., Schwarte-Waldhoff, I. PLoS. One. (2014) [Pubmed]
  13. FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation. Ahmed, A.F., de Bock, C.E., Lincz, L.F., Pundavela, J., Zouikr, I., Sontag, E., Hondermarck, H., Thorne, R.F. Cell. Mol. Life. Sci. (2015) [Pubmed]
  14. Refined localization of the FAT1 quantitative trait locus on pig chromosome 4 by marker-assisted backcrossing. Berg, F., Stern, S., Andersson, K., Andersson, L., Moller, M. BMC Genet. (2006) [Pubmed]
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