FERM‐containing protein FRMD5 is a p120‐catenin interacting protein that regulates tumor progression

Wang, Tao; Pei, Xuelian; Zhan, Jun; Hu, Jinxia; Yu, Yu; Zhang, Hongquan

doi:10.1016/j.febslet.2012.07.019

Cited by 21 publications

(25 citation statements)

References 22 publications

(28 reference statements)

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“…Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. Likewise, FRMD5 encodes FERM-containing protein FRMD5, a p120-catenin interacting protein, regulates lipid metabolic progression26. Our study is the first one carried out in a south Chinese population and the first to find a significant association between this integrative variants, haplotype and diplotypes of the CAPN3 and FRMD5 with lipid variables.…”

Section: Discussionmentioning

confidence: 70%

Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables

Guo

Yin

Pan

et al. 2017

Sci Rep

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To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables. Significant associations with low-density lipoprotein cholesterol and apolipoprotein (Apo) B were found. Linkage disequilibrium with each other showed the haplotype-phenotype associations with triglyceride and ApoA1. This study also suggested pleiotropic associations of the CAPN3-FRMD5 diplotypes with lipid variables. As potential confounders, diastolic blood pressure (DBP) and BMI were significantly associated with lipid variables. We conclude that integrative variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908, as well as DBP and BMI are associated with serum lipid variables in the Jing and Han populations.

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Section: Discussionmentioning

confidence: 70%

Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables

Guo

Yin

Pan

et al. 2017

Sci Rep

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“…Staining with p120 was noticeably reduced by varying degrees in all tumors from the Apc 1638N/+ control group as compared with WT tissue (e.g., Figure 1C) and further reduced in tumors from the TAM-treated cohort β-Catenin functionally links the complex to the actin cytoskeleton via recruitment of α-catenin (20-23), a vinculin-like actin-binding protein. On the other hand, p120 directly stabilizes and retains E-cadherin at the cell surface by suppressing E-cadherin endocytosis (19,(24)(25)(26) and coordinates local interactions with the cytoskeleton through recruitment of various RhoGTPase modulators (e.g., RhoGEFs, RhoGAPs, Rho kinase 1 [ROCK1], FRMD5) (27)(28)(29)(30). Other important signaling systems that interface physically and/or functionally with the E-cadherin complex include the Wnt pathway (e.g., APC, β-catenin) (31), the HIPPO pathway (including downstream effectors YAP and TAZ) (32,33), receptor tyrosine kinase (RTK) pathways (e.g., EGFR and downstream effectors) (34)(35)(36), the TGFβRII pathway (37), and NF-κB signaling (38,39).…”

Section: P120 Functions As An Obligatory Haploinsufficient Tumor Suppmentioning

confidence: 99%

p120-Catenin is an obligate haploinsufficient tumor suppressor in intestinal neoplasia

Short¹,

Kondo²,

Smalley-Freed³

et al. 2017

Journal of Clinical Investigation

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IntroductionThe vast majority of human colorectal cancer (CRC) is triggered by inactivation of the tumor suppressor adenomatous polyposis coli (APC) in one of several intestinal stem cells (ISCs) present in each intestinal crypt. The result is unscheduled translocation of β-catenin to the nucleus where tumorigenesis is initiated via interaction with the transcription factor TCF4 and unregulated transactivation of Wnt pathway target genes (e.g., AXIN2, MYC) (1-4). The ISC contributes several stem cell-restricted properties (e.g., self-renewal, mesenchymal characteristics) that are hijacked by the constitutively activated Wnt pathway and are essential for tumor initiation. Progression to malignancy involves subsequent genetic and epigenetic alterations, including mutations in genes such as KRAS, SMAD4, and TP53, which are frequently targeted in CRC, and a much larger number of less frequently mutated genes uncovered recently by whole genome sequencing. The transition to malignancy is often accompanied by the onset of metastasis, a phenomenon responsible for most cancer-related mortality and frequently linked to genetic and/or epigenetic dysregulation of the cell-cell adhesion receptor epithelial cadherin (E-cadherin) (5-8).E-cadherin is widely regarded as the principle organizer of the epithelial phenotype (9, 10). It functions as a classic tumor suppressor in diffuse gastric cancer (11) and lobular carcinoma of the breast (12), where germline mutations in the E-cadherin gene (CDH1) are responsible for familial inheritance of one mutant allele. Early loss of the second allele (i.e., loss of heterozygosity [LOH]) then plays a causal role in tumorigenesis (11)(12)(13). In the vast majority of epithelial cancers, however, E-cadherin is considered a metastasis suppressor because it is downregulated in advanced tumors and plays a causal role in the transition to metastasis (5,7,(14)(15)(16). Although factors underpinning the distinct differences in timing of E-cadherin loss between these groups are not understood, the former is frequently irreversible (e.g., gene mutation) while the latter often occurs by epithelial-to-mesenchymal transition (EMT) and is later reversed during colonization of distant sites (17).As with all classical cadherins, E-cadherin mediates specific adhesion of adjacent cells via homophilic interaction between extracellular domains (9). Strong E-cadherin-mediated adhesion, however, is absolutely dependent upon formation of a multimeric complex with 3 cytoplasmic binding partners, namely α-, β-, and p120-catenins (p120) (9,18). All members of the classical cadherin family, in fact, use these same core components to organize the actin cytoskeleton and coordinate signaling (9, 19). p120-Catenin (p120) functions as a tumor suppressor in intestinal cancer, but the mechanism is unclear. Here, using conditional p120 knockout in Apc-sensitized mouse models of intestinal cancer, we have identified p120 as an "obligatory" haploinsufficient tumor suppressor. Whereas monoallelic loss of p120 was associated wi...

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“…This indirect effect of p120cate-nin could be cell-type specific as the expression of a p120catenin mutant unable to regulate RhoA in endothelial cells has no effect on VE-cadherin endocytosis [52]. Finally, cadherin-bound p120catenin associates with FERM-domain containing proteins (EPB4125 and FRMD5) that modulate cadherin stability at the plasma membrane [61,62].…”

Section: Membrane-associated P120catenin and The Regulation Of Adherementioning

confidence: 99%

p120catenin alteration in cancer and its role in tumour invasion

Péglion

Etienne-Manneville

2013

Phil. Trans. R. Soc. B

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Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.

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FERM‐containing protein FRMD5 is a p120‐catenin interacting protein that regulates tumor progression

Cited by 21 publications

References 22 publications

Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables

Integrative variants, haplotypes and diplotypes of the CAPN3 and FRMD5 genes and several environmental exposures associate with serum lipid variables

p120-Catenin is an obligate haploinsufficient tumor suppressor in intestinal neoplasia

p120catenin alteration in cancer and its role in tumour invasion

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