Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cadherin superfamily members play an important role in mediating cell-cell contact and adhesion (Takeichi, M., 1991. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451-1455). A distinct subfamily, neither belonging to the classical or protocadherins includes Fat, the largest member of the cadherin super-family. Fat was originally identified in Drosophila. Subsequently, orthologues of Fat have been described in man (Dunne, J., Hanby, A. M., Poulsom, R., Jones, T. A., Sheer, D., Chin, W. G., Da, S. M., Zhao, Q., Beverley, P. C., Owen, M. J., 1995. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics 30, 207-223), rat (Ponassi, M., Jacques, T. S., Ciani, L., ffrench, C. C., 1999. Expression of the rat homologue of the Drosophila fat tumour suppressor gene. Mech. Dev. 80, 207-212) and mouse (Cox, B., Hadjantonakis, A. K., Collins, J. E., Magee, A. I., 2000. Cloning and expression throughout mouse development of mfat1, a homologue of the Drosophila tumour suppressor gene fat [In Process Citation]. Dev. Dyn. 217, 233-240). In Drosophila, Fat has been shown to play an important role in both planar cell polarity and cell boundary formation during development. In this study we describe the characterization of zebrafish Fat, the first non-mammalian, vertebrate Fat homologue to be identified. The Fat protein has 64% amino acid identity and 80% similarity to human FAT and an identical domain structure to other vertebrate Fat proteins. During embryogenesis fat mRNA is expressed in the developing brain, specialised epithelial surfaces the notochord, ears, eyes and digestive tract, a pattern similar but distinct to that found in mammals.
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PMID:Cloning and expression of the large zebrafish protocadherin gene, Fat. 1574 76

Recent studies have identified FAT tumour suppressor homologue 4 (FAT4), an essential component of adherents junctions, involved in several cancers. However, its role in endometrial cancer (EC) remains unclear. In this study, we first analyzed the association between FAT4 expression and tumour stage, tumour type, and patient prognosis in 552 tumour samples and 35 non-tumour samples from The Cancer Genome Atlas (TCGA) database. The association of decreased FAT4 expression with advanced signature (lymph node metastasis, lymphovascular invasion and muscular infiltration) in EC patients was also confirmed by our own dataset. Stable FAT4 Knockdown promoted EC cell lines proliferation and invasion. FAT4 overexpression inhibited the parental cell phenotype. FAT4 silencing resulted in decreased phosphorylation of the LATS1/2 and YAP while increased YAP nuclear translocation which was associated with the promotion of proliferation and invasion. PCR array analysis of the negative control and shFAT4 HEC-1B cell lines revealed that the deubiquitinating enzyme USP51 was a FAT4 interacting target gene. Ablating USP51 by shRNA decreased cellular FAT4 protein level while overexpression of USP51 increased FAT4 protein level. Coimmunoprecipitation confirmed the direct binding of FAT4 and USP51 which was essential for FAT4's function in EC. The growth inhibitory effect of FAT4 was also attenuated by USP51 down-regulation. In conclusion, suppression of FAT4 by inactivation of deubiquitinating enzyme USP51 promoted proliferation and invasion of EC cells via inhibiting Hippo pathway.
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PMID:FAT4-USP51 complex regulates the proliferation and invasion of endometrial cancer via Hippo pathway. 3121 54