Function and cancer genomics of FAT family genes (review).
Function and cancer genomics of FAT family genes (review).
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DOI：
10.3892/ijo.2012.1669
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发表时间：
2012-12
影响因子：
5.2
通讯作者：
Katoh M
中科院分区：
文献类型：
--
作者：
Katoh M
FAT1、FAT2、FAT3和FAT4是果蝇脂肪的人类同源物，参与肿瘤抑制和平面细胞极性(PCP)。FAT1和FAT4经历了Furin的第一次蛋白水解性切割，并被预测经历了γ分泌酶的第二次切割以释放胞内结构域。ENA/VAPS与FAT1结合可诱导肌动蛋白在片层和丝状足端聚合，促进细胞迁移，而Scribble与FAT1结合可诱导YAP1的磷酸化和功能抑制，从而抑制细胞生长。FAT1在口腔癌中由于纯合缺失或表观遗传沉默而被抑制，在浸润性乳腺癌中优先下调。另一方面，FAT1在白血病中表达上调，伴有FAT1上调的Preb-ALL患者预后较差。FAT4直接与MPDZ/MUPP1相互作用，募集膜相关鸟苷酸激酶MPP5/PALS1。FAT4参与维持PCP和抑制细胞增殖。FAT4mRNA在乳腺癌和肺癌中由于启动子高甲基化而被抑制。FAT4基因在黑色素瘤、胰腺癌、胃癌和肝细胞癌等多种人类肿瘤中反复突变。FAT1和FAT4通过激活Hippo信号抑制肿瘤生长，而FAT1通过诱导肌动蛋白聚合促进肿瘤迁移。FAT1以一种上下文依赖的方式抑制肿瘤或致癌，而FAT4则是肿瘤抑制。FAT1、FAT2、FAT3、FAT4、FRMD1、FRMD6、NF2、WWC1、WWC2、SAV1、STK3、STK4、MOB1A、MOB1B、LATS1、LATS2、YAP1和WWTR1/TAZ基因的拷贝数变异、易位和点突变在不同类型的人类肿瘤中有重要意义。由于YAP1和WWTR1位于黏附、GPCR、RTK和干细胞信号网络的十字路口，在个体化医学时代，脂肪信号级联的肿瘤基因组学可以应用于诊断、预后和治疗。
FAT1, FAT2, FAT3 and FAT4 are human homologs of Drosophila Fat, which is involved in tumor suppression and planar cell polarity (PCP). FAT1 and FAT4 undergo the first proteolytic cleavage by Furin and are predicted to undergo the second cleavage by γ-secretase to release intracellular domain (ICD). Ena/VAPS-binding to FAT1 induces actin polymerization at lamellipodia and filopodia to promote cell migration, while Scribble-binding to FAT1 induces phosphorylation and functional inhibition of YAP1 to suppress cell growth. FAT1 is repressed in oral cancer owing to homozygous deletion or epigenetic silencing and is preferentially downregulated in invasive breast cancer. On the other hand, FAT1 is upregulated in leukemia and prognosis of preB-ALL patients with FAT1 upregulation is poor. FAT4 directly interacts with MPDZ/MUPP1 to recruit membrane-associated guanylate kinase MPP5/PALS1. FAT4 is involved in the maintenance of PCP and inhibition of cell proliferation. FAT4 mRNA is repressed in breast cancer and lung cancer due to promoter hypermethylation. FAT4 gene is recurrently mutated in several types of human cancers, such as melanoma, pancreatic cancer, gastric cancer and hepatocellular carcinoma. FAT1 and FAT4 suppress tumor growth via activation of Hippo signaling, whereas FAT1 promotes tumor migration via induction of actin polymerization. FAT1 is tumor suppressive or oncogenic in a context-dependent manner, while FAT4 is tumor suppressive. Copy number aberration, translocation and point mutation of FAT1, FAT2, FAT3, FAT4, FRMD1, FRMD6, NF2, WWC1, WWC2, SAV1, STK3, STK4, MOB1A, MOB1B, LATS1, LATS2, YAP1 and WWTR1/TAZ genes should be comprehensively investigated in various types of human cancers to elucidate the mutation landscape of the FAT-Hippo signaling cascades. Because YAP1 and WWTR1 are located at the crossroads of adhesion, GPCR, RTK and stem-cell signaling network, cancer genomics of the FAT signaling cascades could be applied for diagnostics, prognostics and therapeutics in the era of personalized medicine.
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影响因子：
3.7
作者：
Djiane A;Mlodzik M
通讯作者：
Mlodzik M
DOI：
10.1083/jcb.200508121
发表时间：
2006-05-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hou R;Liu L;Anees S;Hiroyasu S;Sibinga NE
通讯作者：
Sibinga NE
四关节是一种高尔基激酶，可磷酸化钙粘蛋白结构域的子集。
影响因子：
56.9
作者：
Ishikawa, Hiroyuki O.;Takeuchi, Hideyuki;Haltiwanger, Robert S.;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
DOI：
10.1083/jcb.200811030
发表时间：
2009-06-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ishiuchi T;Misaki K;Yonemura S;Takeichi M;Tanoue T
通讯作者：
Tanoue T
影响因子：
56.9
作者：
Bosveld, Floris;Bonnet, Isabelle;Bellaiche, Yohanns
通讯作者：
Bellaiche, Yohanns