Zinc dysregulation in cancers and its potential as a therapeutic target

Wang, Jie; Zhao, Huanhuan; Xu, Zhelong; Cheng, Xinxin

doi:10.20892/j.issn.2095-3941.2020.0106

Cited by 83 publications

(72 citation statements)

References 120 publications

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“…Overexpression, mutations and epigenetic silencing of ADAMTS genes have been reported in different tumours 32 . SLC30A10 is a zinc transporter maintaining zinc homeostasis, which when dysregulated can result in cancer initiation and progression 33 . FGFR4 plays a critical role in embryonic development, tissue repair, tumour angiogenesis and progression 34 .…”

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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“…[24] Other members of ZIPs family have also been con rmed to promote tumor development through the above signaling pathways. [7,20] In addition, ZIP7 plays an important role in maintenance the function state of endoplasmic reticulum (ER). Knockdown or knockout the expression of ZIP7 could induce ER stress and impact protein transport.…”

Section: Discussionmentioning

confidence: 99%

“…[6] Zinc dysregulation and ZIPs abnormal expressions are related to the malignant biological behaviors of various tumors, and are considered as potential therapeutic targets. [7] For esophageal cancer, high expression of ZIP5 or ZIP6 were highly responsible for poor prognosis, and down-regulation of these gene expressions signi cantly inhibited the progression of the disease. [8,9] ZIP4 was signi cantly overexpressed in pancreatic and nasopharyngeal cancer tissue, which was implicated in chemoresistance and radioresistance.…”

Section: Introductionmentioning

confidence: 99%

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

Nie

Sun

Pan

et al. 2021

Preprint

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Background: Irradiation-induced radioresistance often leads to the therapeutic failure of colon cancer. By regulating the redistribution of intracellular zinc, ZIP7 plays a dominating role in the activation of many critical signaling pathways in the progression of tumors. However, the relationship between ZIP7 and radioresistance is still unclear. Methods: ZIP7 expression of colon cancer was evaluated by analyzing public data from the GEPIA and CPTAC databases and validated based on immunohistochemistry (IHC) staining. Clonogenic survival assay was employed to examine the influence of intracellular zinc interference and ZIP7 knockdown on radioresistance of colon cancer, based on radioresistant colon cancer cells. At last, Western blot was performed to preliminarily explore the potential mechanisms. Results: ZIP7 was significantly upregulated in human colon cancers compared with adjacent normal tissues. ZIP7 knockdown could significantly reduce the radioresistance of colon cancer cells, while transmembrane ionophore of zinc could partially reverse this effect. In terms of mechanisms, ZIP7 knockdown significantly reversed the radiation-induced expression of elevated ZEB1 and down-regulated E-cadherin through regulating zinc. Conclusion: ZIP7 is crucial to maintain radioresistance of colon cancer cells through regulation of zinc distribution, and at least partially by maintenance of epithelial-mesenchymal transition (EMT).

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“…Accumulative studies support the fact that the disturbance of zinc homeostasis is associated with various diseases, including Alzheimer’s disease, diabetes, and cancer. Intracellular zinc dyshomeostasis induced by the dysfunction of zinc transporters, especially ZIP transporters, is found to be involved in the development and progression of several human malignancies [ 6 , 7 ]. However, there is still limited mechanistic information available about the relationships between zinc dyshomeostasis and ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway

Cheng

Wang

Liu

et al. 2021

J Exp Clin Cancer Res

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Background Zinc transporters have been found to be associated with the pathogenesis of numerous human diseases including cancer. As the most lethal gynecologic malignancy, ovarian cancer is characterized by rapid progression and widespread metastases. However, the function and underlying mechanism of zinc transporters in ovarian cancer metastasis remain unclear. Methods The relationship between zinc transporter gene expressions and clinical outcomes of ovarian cancer was assessed with the online database Kaplan-Meier plotter (http://kmplot.com/analysis/). Immunohistochemistry was performed to investigate the prognostic importance of ZIP13. The expression of ZIP13 in ovarian cancer cell lines was depleted to explore its effect on proliferation, adhesion, migration, and invasion both in vitro and in vivo assays. RNA-Seq, quantitative RT-PCR, and western blot analysis were performed to explore ZIP13-regulated downstream target genes. Results The expressions of several zinc transporters were highly associated the clinical outcomes of ovarian cancer patients. Among them, high ZIP13 expression was an independent prognostic factor for poor survival in patients with ovarian cancer. ZIP13 knockout suppressed the malignant phenotypes of ovarian cancer cells both in vitro and in vivo. Further investigation revealed that ZIP13 regulated intracellular zinc distribution and then affected the expressions of genes involved in extracellular matrix organization and cytokine-mediated signaling pathway. This led to the activation of Src/FAK pathway with increased expressions of pro-metastatic genes but decreased expressions of tumor suppressor genes. Conclusions ZIP13 is shown to be a novel driver of metastatic progression by modulating the Src/FAK signaling pathway, which may serve as a promising biomarker for prognostic evaluation and targeted therapy in ovarian cancer.

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Zinc dysregulation in cancers and its potential as a therapeutic target

Cited by 83 publications

References 120 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

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway

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