Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial–mesenchymal transition: Partial mediation by the transcription factor NFAT<sub>1</sub>

Dai, Weiqi; Wang, Fan; He, Lei; Lin, Cui-Wu; Wu, Shu-Mei; Chen, Ping; Zhang, Yan; Miao, Song; Wu, Dong; Wang, Chengfen; Lü, Jie; Zhou, Yingqun; Xu, Xuanfu; Xu, Ling; Guo, Chuanyong

doi:10.1002/mc.22100

Cited by 88 publications

(47 citation statements)

References 39 publications

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“…Over the course of two decades of research, a large number of studies have established that in addition to cellautonomous cancer hallmarks such as differentiation ( 58,(103)(104)(105)(106), survival (107)(108)(109)(110)(111)(112), proliferation ( 58,(113)(114)(115)(116), and migration/metastatic behavior ( 50, 74,92,[117][118][119][120][121][122], the aberrant expression/amplifi cation of ATX activity can also dysregulate multiple cancer pathobiology systemic hallmarks including angiogenesis ( 119,123 ), metabolic homeostasis ( 56-59, 104, 124, 125 ), and immune system function ( 126 ).…”

Section: Role In Physiology and Cancer Pathophysiologymentioning

confidence: 99%

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Federico

Jeong

Vellano

et al. 2016

Journal of Lipid Research

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a 125 kDa glycoprotein composed of 915 amino acids ( 1 ). Because it promoted chemotaxis on melanoma cells in an autocrine fashion, the protein was aptly named auto-taxin. Four years after the discovery of the fi rst variant, now commonly referred to as ATX ␣ , or melanoma ATX, a second isoform was cloned by the same team from the teratocarcinoma cell line, Ntera2D1. This polypeptide shared 94% identity with the melanoma protein and was immediately recognized as the alternatively spliced product of the same gene ( 2 ).The initial characterization of the fi rst isoform revealed that ATX biological activity was sensitive to pertussis toxin treatment. Furthermore, not only did the polypeptide share close homology with the murine pyrophosphatase/ type I phosphodiesterase (PDE) PC-1, including a threonine residue crucial for PDE enzymatic activity, but it was also able to hydrolyze PDE substrates in vitro ( 3 ). The confi rmation that ATX was an enzyme came when a new PDE, the PDE1/nucleotide pyrophosphatase (PD-1 ␣ /PDNP 2), was cloned from a cDNA library of human retina and found to be identical to the sequence of melanoma ATX ␣ with the exception of a missing stretch of 52 amino acids encoded by exon 12 in the central region of the open reading frame. The transcript of this variant, now frequently referred to as ATX ␤ , or teratoma ATX, produced a 863 amino acid polypeptide chain with a mass of 99,034 Da ( 4 ), and was independently isolated a few years later in mouse tissues ( 5 ). The third ATX isoform was detected for the fi rst time in rat brain, but was originally designated as PD-I ␣ , a brain-specifi c PDE I/nucleotide pyrophosphatase ( 6 ). Further research showed that PD-I ␣ was identical to ATX ␤ teratoma protein, except for the presence of an additional stretch of 25 amino acids encoded by an alternatively Abstract The ectonucleotide pyrophosphatase/phosphodiesterase type 2, more commonly known as autotaxin (ATX), is an ecto-lysophospholipase D encoded by the human ENNP2 gene. ATX is expressed in multiple tissues and participates in numerous key physiologic and pathologic processes, including neural development, obesity, infl ammation, and oncogenesis, through the generation of the bioactive lipid, lysophosphatidic acid. Overwhelming evidence indicates that altered ATX activity leads to oncogenesis and cancer progression through the modulation of multiple hallmarks of cancer pathobiology. Here, we review the structural and catalytic characteristics of the ectoenzyme, how its expression and maturation processes are regulated, and how the systemic integration of its pleomorphic effects on cells and tissues may contribute to cancer initiation, progression, and therapy. Additionally, the up-to-date spectrum of the most frequent ATX genomic alterations from The Cancer Genome Atlas project is reported for a subset of cancers. ( Fig. 1 ). In 1992, the fi rst alternatively spliced isoform was cloned from the melanoma cell line, A2058, and characterized as STRUCTURE AND ENZYMATIC ACTIVITY ATX belongs to the nuc...

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Section: Role In Physiology and Cancer Pathophysiologymentioning

confidence: 99%

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Federico

Jeong

Vellano

et al. 2016

Journal of Lipid Research

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“…According to this concept, NFATs or NFAT binding partners may serve as better drug targets. Many compounds and drugs with this feature have been reported, including digitoxin, zoledronic acid, and genistein [37,132,133]. These compounds all have good antineoplastic effects in various tumor types, but the molecular mechanisms have not been well studied.…”

Section: Targeting the Nfat Pathway For Cancer Therapymentioning

confidence: 99%

Nuclear factor of activated T cells in cancer development and treatment

et al. 2015

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Since nuclear factor of activated T cells (NFAT) was first identified as a transcription factor in T cells, various NFAT isoforms have been discovered and investigated. Accumulating studies have suggested that NFATs are involved in many aspects of cancer, including carcinogenesis, cancer cell proliferation, metastasis, drug resistance and tumor microenvironment. Different NFAT isoforms have distinct functions in different cancers. The exact function of NFAT in cancer or the tumor microenvironment is context dependent. In this review, we summarize our current knowledge of NFAT regulation and function in cancer development and treatment. NFATs have emerged as a potential target for cancer prevention and therapy.

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“…During embryonic development and adulthood, intracellular Notch signaling is required for cell specification, lineage commitment and maintenance of progenitor cells (7), in particular in the control of endothelial cell differentiation, arteriovenous specification and vascular development (8).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic role of the Notch pathway in primary liver cancer

et al. 2016

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Abstract. Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression.

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Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial–mesenchymal transition: Partial mediation by the transcription factor NFAT₁

Cited by 88 publications

References 39 publications

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Nuclear factor of activated T cells in cancer development and treatment

Oncogenic role of the Notch pathway in primary liver cancer

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Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial–mesenchymal transition: Partial mediation by the transcription factor NFAT1

Cited by 88 publications

References 39 publications

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease Autotaxin, a lysophospholipase D with pleomorphic effects in oncogenesis and cancer progression

Nuclear factor of activated T cells in cancer development and treatment

Oncogenic role of the Notch pathway in primary liver cancer

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Genistein inhibits hepatocellular carcinoma cell migration by reversing the epithelial–mesenchymal transition: Partial mediation by the transcription factor NFAT₁