The Eya phosphatase: Its unique role in cancer

Zhou, Hengbo; Zhang, Lingdi; Vartuli, Rebecca L.; Ford, Heide L.; Zhao, Rui

doi:10.1016/j.biocel.2017.09.001

Cited by 30 publications

(23 citation statements)

References 90 publications

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“…FGFR4 plays a critical role in embryonic development, tissue repair, tumour angiogenesis and progression 34 . EYA1-4 proteins can influence tumour progression through several mechanisms 35 . Homeobox ( HOX ) genes code transcription factors with DNA-binding activity, which regulate the formation of axial patterns and body shape during embryogenesis and have been implicated in cancer development 36 .…”

Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

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Section: Discussionmentioning

confidence: 99%

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

Christakoudi

Εvangelou

Riboli

et al. 2021

Sci Rep

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“…This is in contrast to data showing that Pin1 promotes PP2A dephosphorylation of pSer62 [104]. By preventing the degradation of c-Myc, Eya1 functions as an oncogene; its PTP activity is also oncogenic (Reviewed in [105]). We await a complete understanding of the coordinated interplay among these various PTMs on c-Myc in normal physiology but it is clear that the deregulation of one or more of these processes can tip the balance toward tumor promotion.…”

Section: C-mycmentioning

confidence: 90%

The impact of phosphatases on proliferative and survival signaling in cancer

Narla

Sangodkar

Ryder

2018

Cell. Mol. Life Sci.

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The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role. In oncology, these efforts led to breakthroughs that have dramatically altered the course of certain diseases and directed vast resources toward the development of additional kinase-targeted therapies. Yet, more recent scientific efforts have demonstrated a prominent and sometimes driving role for phosphatases across numerous malignancies. This maturation of the phosphatase field has brought with it the promise of further therapeutic advances in the field of oncology. In this review, we discuss the role of phosphatases in the regulation of cellular proliferation and survival signaling using the examples of the MAPK and PI3K/AKT pathways, c-Myc and the apoptosis machinery. Emphasis is placed on instances where these signaling networks are perturbed by dysregulation of specific phosphatases to favor growth and persistence of human cancer.

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“…Structural biology is very important for understanding the function of eye absent (EYA) proteins and provides valuable insights into designing chemical probes to explore their function. EYA proteins (EYA1-4) are a class of proteins binding to the sine oculis homeobox (Six) family of homeobox proteins to activate transcriptions [ 140 , 141 , 142 , 143 ]. Six1 and EYA proteins are critical in embryogenesis and they are found to be down regulated in normal adult tissues and overexpressed in some cancers [ 144 , 145 ].…”

Section: Allosteric Inhibitors For a Phosphatasementioning

confidence: 99%

Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

Kang

2020

IJMS

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Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

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The Eya phosphatase: Its unique role in cancer

Cited by 30 publications

References 90 publications

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer

The impact of phosphatases on proliferative and survival signaling in cancer

Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

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