ZNT5-6 and ZNT7 play an integral role in protein N-glycosylation by supplying Zn2+ to Golgi α-mannosidase II

Yuasa, Hana; Morino, Naho; Wagatsuma, Takumi; Munekane, Masayuki; Ueda, Sachiko; Matsunaga, Mayu; Uchida, Yasuo; Katayama, Takane; Katoh, Toshihiko; Kambe, Taiho

doi:10.1016/j.jbc.2024.107378

Cited by 2 publications

(2 citation statements)

References 76 publications

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“…ZnT5 and ZnT6 are expressed in the Golgi apparatus and form functional heterodimers [45]. They participate in the biosynthesis of cancer-promoting zinc-requiring ectoenzymes such as alkaline phosphatase (ALP), autotaxin (ATX), or metalloproteinase (MMP-9) [44], and glycoprotein [162]. Depletion of ZnT5-ZnT6 heterodimer (or ZnT7 homodimer) decreases the growth of pancreatic cancer MIA PaCa-2 cells [162].…”

Section: Potential Mechanisms Of Pattern Zip-up/znt-down In Prostate ...mentioning

confidence: 99%

“…They participate in the biosynthesis of cancer-promoting zinc-requiring ectoenzymes such as alkaline phosphatase (ALP), autotaxin (ATX), or metalloproteinase (MMP-9) [44], and glycoprotein [162]. Depletion of ZnT5-ZnT6 heterodimer (or ZnT7 homodimer) decreases the growth of pancreatic cancer MIA PaCa-2 cells [162]. In addition, these ZnTs mobilize zinc to the ER lumen, which is necessary to activate ERp44 [163], a chaperone previously described as a biomarker of prostate cancer [164].…”

Section: Potential Mechanisms Of Pattern Zip-up/znt-down In Prostate ...mentioning

confidence: 99%

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Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review

Acevedo,

Segovia,

de la Fuente-Ortega

2024

Nutrients

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Dysregulation of zinc and zinc transporters families has been associated with the genesis and progression of prostate cancer. The prostate epithelium utilizes two types of zinc transporters, the ZIP (Zrt-, Irt-related Protein) and the ZnTs (Zinc Transporter), to transport zinc from the blood plasma to the gland lumen. ZIP transporters uptake zinc from extracellular space and organelle lumen, while ZnT transporters release zinc outside the cells or to organelle lumen. In prostate cancer, a commonly observed low zinc concentration in prostate tissue has been correlated with downregulations of certain ZIPs (e.g., ZIP1, ZIP2, ZIP3, ZIP14) and upregulations of specific ZnTs (e.g., ZnT1, ZnT9, ZnT10). These alterations may enable cancer cells to adapt to toxic high zinc levels. While zinc supplementation has been suggested as a potential therapy for this type of cancer, studies have yielded inconsistent results because some trials have indicated that zinc supplementation could exacerbate cancer risk. The reason for this discrepancy remains unclear, but given the high molecular and genetic variability present in prostate tumors, it is plausible that some zinc transporters—comprising 14 ZIP and 10 ZnT members—could be dysregulated in others patterns that promote cancer. From this perspective, this review highlights novel dysregulation, such as ZIP-Up/ZnT-Down, observed in prostate cancer cell lines for ZIP4, ZIP8, ZnT2, ZnT4, ZnT5, etc. Additionally, an in silico analysis of an available microarray from mouse models of prostate cancer (Nkx3.1;Pten) predicts similar dysregulation pattern for ZIP4, ZIP8, and ZnT2, which appear in early stages of prostate cancer progression. Furthermore, similar dysregulation patterns are supported by an in silico analysis of RNA-seq data from human cancer tumors available in cBioPortal. We discuss how these dysregulations of zinc transporters could impact zinc supplementation trials, particularly focusing on how the ZIP-Up/ZnT-Down dysregulation through various mechanisms might promote prostate cancer progression.

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Section: Potential Mechanisms Of Pattern Zip-up/znt-down In Prostate ...mentioning

confidence: 99%

Section: Potential Mechanisms Of Pattern Zip-up/znt-down In Prostate ...mentioning

confidence: 99%

Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review

Acevedo,

Segovia,

de la Fuente-Ortega

2024

Nutrients

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Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo

Yuasa,

Miyazaki,

Kido

et al. 2024

The FASEB Journal

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Extracellular hydrolysis of the phosphate esters of B vitamins (B1, B2, and B6) is crucial for their cellular uptake and metabolism. Although a few zinc‐dependent enzymes have been implicated in these processes, their exact mechanisms of action remain largely unknown. This study investigated the potential involvement of phosphate group hydrolyzing enzymes in the hydrolysis of B vitamin phosphate esters. We evaluated enzyme activity in membrane lysates prepared from cells transiently transfected with these enzymes or those endogenously expressing them. Specifically, we investigated how zinc deficiency affects the rate of hydrolysis of B vitamin phosphate esters in cellular lysates. Assessment of the activities of zinc‐dependent ectoenzymes in the lysates prepared from cells cultured in zinc‐deficient conditions and in the serum of rats fed zinc‐deficient diets revealed that zinc deficiency reduced the extracellular hydrolysis activity of B vitamin phosphate esters. Furthermore, our findings explain the similarities between several symptoms of B vitamin and zinc deficiencies. Collectively, this study provides novel insights into the diverse symptoms of zinc deficiency and could guide the development of appropriate clinical strategies.

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ZNT5-6 and ZNT7 play an integral role in protein N-glycosylation by supplying Zn2+ to Golgi α-mannosidase II

Cited by 2 publications

References 76 publications

Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review

Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review

Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo

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