Human Fat2 is localized at immature adherens junctions in epidermal keratinocytes

Matsui, Seiya; Takahashi, Keiichi; Mukoyama, Yohei; Matsuyoshi, Norihisa

doi:10.1016/j.jdermsci.2007.07.010

Cited by 12 publications

(11 citation statements)

References 10 publications

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“…Second, we then performed a phagocytic gold motility assay, which evaluates random and non-vectorial motility called chemokinesis. We previously have reported that Fat2 and actin filaments are structurally related, as shown by experiments, using an inhibitor of actin polymerization [3]. Knockdown of Fat2 also decreased the phagocytic cell migration (Fig.…”

Section: Knockdown Of Fat2 By Sirna Inhibits the Migration Of Human Ssupporting

confidence: 58%

“…Transfection of HSC-1 cells with 10 nM Fat2-specific siRNA or nonspecific control siRNA in RNAi MAX (Invitrogen) was performed for 48 h. Then immunoblotting using the generated anti-human Fat2 polyclonal antibody (1:100 dilution) was performed as previously described [3]. Nonspecific siRNA, which was not homologous to any human gene, was used as a negative control (Invitrogen).…”

Section: Knockdown Of Fat2 By Sirna Inhibits the Migration Of Human Smentioning

confidence: 99%

“…In the present study, activation of activating transcription factor-2 (ATF2) and signal transducer and activator of transcription-3 (STAT3) are examined in these common cutaneous malignancies because extracellular signal-regulated kinases (ERK) and AP-1 have been shown to play important roles in the development of SCC and/or BCC [1][2][3], and ATF2-and STAT3-pathways could be significantly related to these transcription-associated molecules. In the present study, activation of activating transcription factor-2 (ATF2) and signal transducer and activator of transcription-3 (STAT3) are examined in these common cutaneous malignancies because extracellular signal-regulated kinases (ERK) and AP-1 have been shown to play important roles in the development of SCC and/or BCC [1][2][3], and ATF2-and STAT3-pathways could be significantly related to these transcription-associated molecules.…”

Section: Letter To the Editormentioning

confidence: 99%

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Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells

Matsui

Takahashi

Mukoyama

et al. 2008

Journal of Dermatological Science

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Section: Knockdown Of Fat2 By Sirna Inhibits the Migration Of Human Ssupporting

confidence: 58%

Section: Knockdown Of Fat2 By Sirna Inhibits the Migration Of Human Smentioning

confidence: 99%

Section: Letter To the Editormentioning

confidence: 99%

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Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells

Matsui

Takahashi

Mukoyama

et al. 2008

Journal of Dermatological Science

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“…FAT2 encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development [37]. FAT2 is a member of the cadherin superfamily and most likely functions as a cell adhesion molecule [38]. FAT2 was frequently mutated in clear cell renal cell carcinoma [39, 40].…”

Section: Resultsmentioning

confidence: 99%

A comprehensive genomic pan-cancer classification using The Cancer Genome Atlas gene expression data

et al. 2017

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BackgroundThe Cancer Genome Atlas (TCGA) has generated comprehensive molecular profiles. We aim to identify a set of genes whose expression patterns can distinguish diverse tumor types. Those features may serve as biomarkers for tumor diagnosis and drug development.MethodsUsing RNA-seq expression data, we undertook a pan-cancer classification of 9,096 TCGA tumor samples representing 31 tumor types. We randomly assigned 75% of samples into training and 25% into testing, proportionally allocating samples from each tumor type.ResultsWe could correctly classify more than 90% of the test set samples. Accuracies were high for all but three of the 31 tumor types, in particular, for READ (rectum adenocarcinoma) which was largely indistinguishable from COAD (colon adenocarcinoma). We also carried out pan-cancer classification, separately for males and females, on 23 sex non-specific tumor types (those unrelated to reproductive organs). Results from these gender-specific analyses largely recapitulated results when gender was ignored. Remarkably, more than 80% of the 100 most discriminative genes selected from each gender separately overlapped. Genes that were differentially expressed between genders included BNC1, FAT2, FOXA1, and HOXA11. FOXA1 has been shown to play a role for sexual dimorphism in liver cancer. The differentially discriminative genes we identified might be important for the gender differences in tumor incidence and survival.ConclusionsWe were able to identify many sets of 20 genes that could correctly classify more than 90% of the samples from 31 different tumor types using TCGA RNA-seq data. This accuracy is remarkable given the number of the tumor types and the total number of samples involved. We achieved similar results when we analyzed 23 non-sex-specific tumor types separately for males and females. We regard the frequency with which a gene appeared in those sets as measuring its importance for tumor classification. One third of the 50 most frequently appearing genes were pseudogenes; the degree of enrichment may be indicative of their importance in tumor classification. Lastly, we identified a few genes that might play a role in sexual dimorphism in certain cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3906-0) contains supplementary material, which is available to authorized users.

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“…The vertebrate Fat cadherins [1] comprise a family of four structurally similar genes homologous to the Drosophila tumour suppressor Fat cadherin [2] and the related Fat2 (Ft2) gene [3]. Knockout of the Fat1 gene in mice caused lethal defects in kidney development with a proportion of Fat1 -/-newborns displaying deformed eyes and craniofacial malformations, while others were cannibalised at birth due to appearance of exencephaly [4].…”

Section: Introductionmentioning

confidence: 99%

FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation

Ahmed

Bock

Lincz

et al. 2015

Cell. Mol. Life Sci.

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The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.

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Human Fat2 is localized at immature adherens junctions in epidermal keratinocytes

Cited by 12 publications

References 10 publications

Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells

Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells

A comprehensive genomic pan-cancer classification using The Cancer Genome Atlas gene expression data

FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation

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