Zinc finger MYND‐type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor‐A expression

Kuroyanagi, Junya; Zhang, Beibei; Ariyoshi, Michiko; Umemoto, Noriko; Nishimura, Yuhei; Tanaka, Toshio

doi:10.1016/j.febslet.2014.07.033

Cited by 20 publications

(11 citation statements)

References 44 publications

(44 reference statements)

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“…Our extensive functional studies in multiple ER + and TNBC cell lines in vitro and breast cancer mouse models indicate that ZMYND8 is an oncoprotein in breast cancer. This concept may be extended to prostate cancer because a previous study showed that ZMYND8 increases VEGFA expression and angiogenesis in prostate DU145 xenograft tumors from zebrafish (45). Previous genetic studies identified ZMYND8 fusion proteins in patients with acute erythroid leukemia and breast cancer and they may be pathogenic for the diseases (46,47), also supporting an oncogenic role of ZMYND8 in human cancers.…”

Section: Discussionmentioning

confidence: 91%

ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis

Chen¹,

Zhang

Bao

et al. 2018

Journal of Clinical Investigation

121

154

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Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice. The ZMYND8's oncogenic effect in breast cancer requires HIF-1 and HIF-2. We further showed that ZMYND8 interacts with HIF-1α and HIF-2α and enhances elongation of the global HIF-induced oncogenic genes by increasing recruitment of BRD4 and subsequent release of paused RNA polymerase II in breast cancer cells. ZMYND8 acetylation at lysines 1007 and 1034 by p300 is required for HIF activation and breast cancer progression and metastasis. These findings uncover a primary epigenetic mechanism of HIF activation and HIF-mediated breast cancer progression, and discover a possible molecular target for the diagnosis and treatment of breast cancer.

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Section: Discussionmentioning

confidence: 91%

ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis

Chen¹,

Zhang

Bao

et al. 2018

Journal of Clinical Investigation

121

154

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“…This suggests that TRIM66 may act as an oncoprotein, possibly by suppressing apoptosis while promoting TGFβ 148 . Finally ZMYND8 was recently shown to promote tumour angiogenesis in zebrafish prostate cancer xenografts, as well as in prostate cancer samples from patients 149 .…”

Section: Misexpression Of Brd-containing Proteins In Cancermentioning

confidence: 99%

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Fujisawa

Filippakopoulos

2017

Nat Rev Mol Cell Biol

448

441

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Bromodomains (BRDs) are evolutionarily conserved protein-protein interaction modules that are found in a wide range of proteins with diverse catalytic and scaffolding functions and are present in most tissues. BRDs selectively recognize and bind to acetylated Lys residues - particularly in histones - and thereby have important roles in the regulation of gene expression. BRD-containing proteins are frequently dysregulated in cancer, they participate in gene fusions that generate diverse, frequently oncogenic proteins, and many cancer-causing mutations have been mapped to the BRDs themselves. Importantly, BRDs can be targeted by small-molecule inhibitors, which has stimulated many translational research projects that seek to attenuate the aberrant functions of BRD-containing proteins in disease.

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“…Images were captured using a MZ16F stereoscopic microscope (Leica Microsystems, Wetzlar, Germany) equipped with a DP71 digital camera (Olympus, Tokyo, Japan).For fluorescence imaging, GFP2 (for fli1:egfp) and DsRed (for KOr) filters were selected. Cancer cell proliferation was calculated by the ratio of KOr fluorescence intensity in the tumour area relative to that at day 0using ImageJ software (National Institutes of Health, Bethesda, MD, USA) as described previously [10,22,25].…”

Section: Imagingmentioning

confidence: 99%

“…xenograftzebrafish represent a promising alternative model to study tumour proliferation [7,8], angiogenesis [9,10], metastasis [11,12]and cancer stemness [13,14]. To avoid immune rejection of the xenograft, cancer cell implantationhas been performedat the embryonic stage (24-72 hours post-fertilization, hpf) when the adaptive immune response is not established.Although the sites of haematopoiesis are different between zebrafish and mammals, the cellular and regulatory processes of haematopoiesis,includingfor immune cells, are highly conserved [15,16].…”

Section: Introductionmentioning

confidence: 99%

Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish

Zhang

Hirota

Ariyoshi

et al. 2016

Translational Research

Self Cite

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Immune deficiency or suppression in host animals is an essential precondition for the success of cancer cell xenotransplantation because the host immune system has a tendency to reject implanted cells. However, in such animals, the typical tumor microenvironment seen in cancer subjects does not form because of the lack of normal immunity. Here, we developed a novel zebrafish (Danio rerio) model based on 2 rounds of cancer cell xenotransplantation that achieved cancer-specific immunologic tolerance without immunosuppression. We irradiated human cancer cells (PC-3, K562 and HepG2) to abolish their proliferative abilities and implanted them into zebrafish larvae. These cells survived for 2 weeks in the developing host. Three months after the first implantation, the zebrafish were implanted with the same, but nonirradiated, cell lines. These cancer cells proliferated and exhibited metastasis without immune suppression. To reveal the transcriptional mechanism of this immune tolerance, we conducted dual RNA-seq of the tumor with its surrounding tissues and identified several regulatory zebrafish genes that are involved in immunity; the expression of plasminogen activator, urokinase, and forkhead box P3 was altered in response to immunologic tolerance. In conclusion, this xenograft method has potential as a platform for zebrafish-based anticancer drug discovery because it can closely mimic human clinical cancers without inducing immune suppression.

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Zinc finger MYND‐type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor‐A expression

Cited by 20 publications

References 44 publications

ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis

ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis

Functions of bromodomain-containing proteins and their roles in homeostasis and cancer

Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish

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