HOXB13 downregulates intracellular zinc and increases NF-κB signaling to promote prostate cancer metastasis

Yr, Kim; Ij, Kim; Tw, Kang; Choi, Chan; Kk, Kim; Ms, Kim; Nam, Kwang Il; Jung, Chang-Yeol

doi:10.1038/onc.2013.404

Cited by 64 publications

(61 citation statements)

References 41 publications

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“…Heijmink et al [72] showed that citrate is absent in lymph node metastasis; and this would be indicative of decreased zinc. Kim et al [73] reported that promotion of prostate cancer invasion and metastasis occurs by decreasing intracellular zinc levels. Compelling evidence is also provided by identification of the loss of citrate, zinc, and ZIP1 in the metastatic lymph nodes in TRAMP.…”

Section: Zinc For the Treatment Of Zip1-deficient Prostate Cancermentioning

confidence: 99%

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

Costello

Franklin

2016

Archives of Biochemistry and Biophysics

186

180

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The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, which is achieved by the high cellular zinc level effects on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued.

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Section: Zinc For the Treatment Of Zip1-deficient Prostate Cancermentioning

confidence: 99%

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

Costello

Franklin

2016

Archives of Biochemistry and Biophysics

186

180

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“…Although zinc-transporter 1 might be a target for therapy, currently no drug exists to activate this transporter [123]. Additionally, a low zinc level might be maintained in later stages by HoxB13-mediated induction of the zinc output transporter ZnT4 [186].…”

Section: Genetic Drivers Signaling and Microenvironment In Prostate mentioning

confidence: 99%

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

104

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KEYWORDS:Cancer metabolism, metabolic therapy, tissue specific metabolism, genetic drivers, epigenetic drivers, microenvironment, Warburg effect, reverse Warburg effect, mixed Warburg effect, triple-negative breast cancer, estrogen receptor positive breast cancer; prostate cancer, liver cancer, gluconeogenesis, fatty acid metabolism, glucose metabolism, glutamine metabolism, serine metabolism, metabolic normalization, metabolic depletion ABSTRACTTargeting the metabolism of cancer cells has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor positive breast cancer, early and late stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g. Warburg versus reverse Warburg metabolism). Yet, for each of the cancers their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

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“…A further pro-oncogenic effect of HOXB13 is exerted through the upregulation of zinc transporters that in turn results in lower intracellular zinc concentrations. This reduces the level of inhibitor of NF-κΒ alpha (IκΒα) and promotes NF-κΒα signaling leading to increased invasion and metastasis [52] . Thus, HOXB13 exerts multiple tumor-promoting effects through the regulation of specific target genes.…”

Section: Hox Genes In Prostate Cancermentioning

confidence: 99%

HOX transcription factors and the prostate tumor microenvironment

Morgan¹,

Pandha²

2017

JCMT

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It is now well established that the tumor microenvironment plays an essential role in the survival, growth, invasion, and spread of cancer through the regulation of angiogenesis and localized immune responses. This review examines the role of the HOX genes, which encode a family of homeodomain-containing transcription factors, in the interaction between prostate tumors and their microenvironment. Previous studies have established that HOX genes have an important function in prostate cancer cell survival in vitro and in vivo, but there is also evidence that HOX proteins regulate the expression of genes in the cancer cell that influence the tumor microenvironment, and that cells in the microenvironment likewise express HOX genes that confer a tumor-supportive function. Here we provide an overview of these studies that, taken together, indicate that the HOX genes help mediate cross talk between prostate tumors and their microenvironment. Key words:Prostate cancer, tumor microenvironment, HOX, PBX, metastasis, angiogenesis ABSTRACTArticle history:

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HOXB13 downregulates intracellular zinc and increases NF-κB signaling to promote prostate cancer metastasis

Cited by 64 publications

References 41 publications

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

Organ-Specific Cancer Metabolism and Its Potential for Therapy

HOX transcription factors and the prostate tumor microenvironment

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