Zinc dysregulation in cancers and its potential as a therapeutic target

References

1. 1.↵
   2. Chasapis CT,
   3. Loutsidou AC,
   4. Spiliopoulou CA,
   5. Stefanidou ME.

   Zinc and human health: an update. Arch Toxicol. 2012; 86: 521–34.

   OpenUrlCrossRefPubMed
2. 2.↵
   2. Sensi SL,
   3. Granzotto A,
   4. Siotto M,
   5. Squitti R.

   Copper and zinc dysregulation in Alzheimer’s disease. Trends Pharmacol Sci. 2018; 39: 1049–63.

   OpenUrlCrossRefPubMed
3. 3.
   2. Fukunaka A,
   3. Fujitani Y.

   Role of zinc homeostasis in the pathogenesis of diabetes and obesity. Int J Mol Sci. 2018; 19: 476.

   OpenUrl
4. 4.
   2. Gammoh NZ,
   3. Rink L.

   Zinc in infection and inflammation. Nutrients. 2017; 9: 624.

   OpenUrlCrossRefPubMed
5. 5.↵
   2. Chu A,
   3. Foster M,
   4. Samman S.

   Zinc status and risk of cardiovascular diseases and type 2 diabetes mellitus – a systematic review of prospective cohort studies. Nutrients. 2016; 8: 707.

   OpenUrl
6. 6.↵
   2. Andreini C,
   3. Banci L,
   4. Bertini I,
   5. Rosato A.

   Counting the zinc-proteins encoded in the human genome. J Proteome Res. 2006; 5: 196–201.

   OpenUrlCrossRefPubMedWeb of Science
7. 7.↵
   2. Hojyo S,
   3. Fukada T.

   Zinc transporters and signaling in physiology and pathogenesis. Arch Biochem Biophys. 2016; 611: 43–50.

   OpenUrlCrossRef
8. 8.↵
   2. Wessels I,
   3. Maywald M,
   4. Rink L.

   Zinc as a gatekeeper of immune function. Nutrients. 2017; 9: 1286.

   OpenUrlPubMed
9. 9.↵
   2. Fukada T,
   3. Yamasaki S,
   4. Nishida K,
   5. Murakami M,
   6. Hirano T.

   Zinc homeostasis and signaling in health and diseases: zinc signaling. J Biol Inorg Chem. 2011; 16: 1123–34.

   OpenUrlCrossRefPubMed
10. 10.↵
    2. Jarosz M,
    3. Olbert M,
    4. Wyszogrodzka G,
    5. Mlyniec K,
    6. Librowski T.

    Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology. 2017; 25: 11–24.

    OpenUrl
11. 11.↵
    2. Kambe T,
    3. Tsuji T,
    4. Hashimoto A,
    5. Itsumura N.

    The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol Rev. 2015; 95: 749–84.

    OpenUrlCrossRefPubMed
12. 12.↵
    2. Fukada T,
    3. Kambe T.

    Molecular and genetic features of zinc transporters in physiology and pathogenesis. Metallomics. 2011; 3: 662–74.

    OpenUrlCrossRefPubMedWeb of Science
13. 13.↵
    2. Kambe T.

    Molecular architecture and function of ZnT transporters. Curr Top Membr. 2012; 69: 199–220.

    OpenUrlCrossRefPubMed
14. 14.↵
    2. Weaver BP,
    3. Andrews GK.

    Regulation of zinc-responsive Slc39a5 (Zip5) translation is mediated by conserved elements in the 3’-untranslated region. Biometals. 2012; 25: 319–35.

    OpenUrlCrossRefPubMed
15. 15.↵
    2. Chandler P,
    3. Kochupurakkal BS,
    4. Alam S,
    5. Richardson AL,
    6. Soybel DI,
    7. Kelleher SL.

    Subtype-specific accumulation of intracellular zinc pools is associated with the malignant phenotype in breast cancer. Mol Cancer. 2016; 15: 2.

    OpenUrl
16. 16.↵
    2. Krezel A,
    3. Maret W.

    The functions of metamorphic metallothioneins in zinc and copper metabolism. Int J Mol Sci. 2017; 18: 1237.

    OpenUrl
17. 17.↵
    2. Gunther V,
    3. Lindert U,
    4. Schaffner W.

    The taste of heavy metals: gene regulation by MTF-1. Biochim Biophys Acta. 2012; 1823: 1416–25.

    OpenUrlCrossRefPubMedWeb of Science
18. 18.↵
    2. Prasad AS,
    3. Beck FW,
    4. Doerr TD,
    5. Shamsa FH,
    6. Penny HS,
    7. Marks SC, et al.

    Nutritional and zinc status of head and neck cancer patients: an interpretive review. J Am Coll Nutr. 1998; 17: 409–18.

    OpenUrlPubMedWeb of Science
19. 19.↵
    2. Taccioli C,
    3. Chen H,
    4. Jiang Y,
    5. Liu XP,
    6. Huang K,
    7. Smalley KJ, et al.

    Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature. Oncogene. 2012; 31: 4550–8.

    OpenUrlCrossRefPubMedWeb of Science
20. 20.
    2. Alder H,
    3. Taccioli C,
    4. Chen H,
    5. Jiang Y,
    6. Smalley KJ,
    7. Fadda P, et al.

    Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer. Carcinogenesis. 2012; 33: 1736–44.

    OpenUrlCrossRefPubMedWeb of Science
21. 21.↵
    2. Fong LY,
    3. Taccioli C,
    4. Palamarchuk A,
    5. Tagliazucchi GM,
    6. Jing R,
    7. Smalley KJ, et al.

    Abrogation of esophageal carcinoma development in miR-31 knockout rats. Proc Natl Acad Sci U S A. 2020; 117: 6075–85.

    OpenUrlAbstract/FREE Full Text
22. 22.↵
    2. Lee DH,
    3. Anderson KE,
    4. Harnack LJ,
    5. Folsom AR,
    6. Jacobs DR,
    7. Jr .

    Heme iron, zinc, alcohol consumption, and colon cancer: Iowa Women’s Health Study. J Natl Cancer Inst. 2004; 96: 403–7.

    OpenUrlCrossRefPubMedWeb of Science
23. 23.↵
    2. Ho E.

    Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem. 2004; 15: 572–8.

    OpenUrlCrossRefPubMedWeb of Science
24. 24.↵
    2. Song Y,
    3. Leonard SW,
    4. Traber MG,
    5. Ho E.

    Zinc deficiency affects DNA damage, oxidative stress, antioxidant defenses, and DNA repair in rats. J Nutr. 2009; 139: 1626–31.

    OpenUrlAbstract/FREE Full Text
25. 25.↵
    2. King LE,
    3. Frentzel JW,
    4. Mann JJ,
    5. Fraker PJ.

    Chronic zinc deficiency in mice disrupted T cell lymphopoiesis and erythropoiesis while B cell lymphopoiesis and myelopoiesis were maintained. J Am Coll Nutr. 2005; 24: 494–502.

    OpenUrlPubMedWeb of Science
26. 26.↵
    2. Prasad AS.

    Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000; 182(Suppl 1): S62–8.

    OpenUrlCrossRefPubMedWeb of Science
27. 27.↵
    2. John E,
    3. Laskow TC,
    4. Buchser WJ,
    5. Pitt BR,
    6. Basse PH,
    7. Butterfield LH, et al.

    Zinc in innate and adaptive tumor immunity. J Transl Med. 2010; 8: 118.

    OpenUrlCrossRefPubMed
28. 28.↵
    2. Alam S,
    3. Kelleher SL.

    Cellular mechanisms of zinc dysregulation: a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer. Nutrients. 2012; 4: 875–903.

    OpenUrlCrossRefPubMed
29. 29.↵
    2. Grattan BJ,
    3. Freake HC.

    Zinc and cancer: implications for LIV-1 in breast cancer. Nutrients. 2012; 4: 648–75.

    OpenUrlPubMed
30. 30.↵
    2. Piccinini L,
    3. Borella P,
    4. Bargellini A,
    5. Medici CI,
    6. Zoboli A.

    A case-control study on selenium, zinc, and copper in plasma and hair of subjects affected by breast and lung cancer. Biol Trace Elem Res. 1996; 51: 23–30.

    OpenUrlPubMed
31. 31.↵
    2. Memon AU,
    3. Kazi TG,
    4. Afridi HI,
    5. Jamali MK,
    6. Arain MB,
    7. Jalbani N, et al.

    Evaluation of zinc status in whole blood and scalp hair of female cancer patients. Clin Chim Acta. 2007; 379: 66–70.

    OpenUrlCrossRefPubMedWeb of Science
32. 32.↵
    2. Ros-Bullon MR,
    3. Sanchez-Pedreno P,
    4. Martinez-Liarte JH.

    Serum zinc levels are increased in melanoma patients. Melanoma Res. 1998; 8: 273–7.

    OpenUrlPubMed
33. 33.↵
    2. Navarro Silvera SA,
    3. Rohan TE.

    Trace elements and cancer risk: a review of the epidemiologic evidence. Cancer Causes Control. 2007; 18: 7–27.

    OpenUrlCrossRefPubMedWeb of Science
34. 34.↵
    2. Costello LC,
    3. Franklin RB.

    A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch Biochem Biophys. 2016; 611: 100–12.

    OpenUrlCrossRefPubMed
35. 35.↵
    2. Yildiz A,
    3. Kaya Y,
    4. Tanriverdi O.

    Effect of the interaction between selenium and zinc on DNA repair in association with cancer prevention. J Cancer Prev. 2019; 24: 146–54.

    OpenUrl
36. 36.↵
    2. Prasad AS,
    3. Bao B.

    Molecular mechanisms of zinc as a pro-antioxidant mediator: clinical therapeutic implications. Antioxidants (Basel). 2019; 8: 164.

    OpenUrl
37. 37.↵
    2. Kelleher SL,
    3. McCormick NH,
    4. Velasquez V,
    5. Lopez V.

    Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland. Adv Nutr. 2011; 2: 101–11.

    OpenUrlAbstract/FREE Full Text
38. 38.↵
    2. Franklin RB,
    3. Ma J,
    4. Zou J,
    5. Guan Z,
    6. Kukoyi BI,
    7. Feng P, et al.

    Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J Inorg Biochem. 2003; 96: 435–42.

    OpenUrlCrossRefPubMedWeb of Science
39. 39.↵
    2. Costello LC,
    3. Franklin RB,
    4. Zou J,
    5. Feng P,
    6. Bok R,
    7. Swanson MG, et al.

    Human prostate cancer ZIP1/zinc/citrate genetic/metabolic relationship in the TRAMP prostate cancer animal model. Cancer Biol Ther. 2011; 12: 1078–84.

    OpenUrlCrossRefPubMed
40. 40.↵
    2. Costello LC,
    3. Franklin RB.

    Zinc is decreased in prostate cancer: an established relationship of prostate cancer! J Biol Inorg Chem. 2011; 16: 3–8.
41. 41.↵
    2. Franklin RB,
    3. Feng P,
    4. Milon B,
    5. Desouki MM,
    6. Singh KK,
    7. Kajdacsy-Balla A, et al.

    hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Mol Cancer. 2005; 4: 32.

    OpenUrlCrossRefPubMed
42. 42.↵
    2. Milon BC,
    3. Agyapong A,
    4. Bautista R,
    5. Costello LC,
    6. Franklin RB.

    Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells. Prostate. 2010; 70: 288–96.

    OpenUrlCrossRefPubMedWeb of Science
43. 43.↵
    2. Zou J,
    3. Milon BC,
    4. Desouki MM,
    5. Costello LC,
    6. Franklin RB.

    hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of Ras responsive element binding protein-1 (RREB-1). Prostate. 2011; 71: 1518–24.

    OpenUrlPubMed
44. 44.↵
    2. Desouki MM,
    3. Geradts J,
    4. Milon B,
    5. Franklin RB,
    6. Costello LC.

    hZIP2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands. Mol Cancer. 2007; 6: 37.

    OpenUrlCrossRefPubMedWeb of Science
45. 45.↵
    2. Henshall SM,
    3. Afar DE,
    4. Rasiah KK,
    5. Horvath LG,
    6. Gish K,
    7. Caras I, et al.

    Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer. Oncogene. 2003; 22: 6005–12.

    OpenUrlCrossRefPubMedWeb of Science
46. 46.↵
    2. Singh KK,
    3. Desouki MM,
    4. Franklin RB,
    5. Costello LC.

    Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues. Mol Cancer. 2006; 5: 14.

    OpenUrlCrossRefPubMed
47. 47.↵
    2. Costello LC,
    3. Feng P,
    4. Milon B,
    5. Tan M,
    6. Franklin RB.

    Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve. Prostate Cancer Prostatic Dis. 2004; 7: 111–7.

    OpenUrlCrossRefPubMedWeb of Science
48. 48.↵
    2. Feng P,
    3. Li TL,
    4. Guan ZX,
    5. Franklin RB,
    6. Costello LC.

    Direct effect of zinc on mitochondrial apoptogenesis in prostate cells. Prostate. 2002; 52: 311–8.

    OpenUrlCrossRefPubMedWeb of Science
49. 49.↵
    2. Feng P,
    3. Li T,
    4. Guan Z,
    5. Franklin RB,
    6. Costello LC.

    The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant prostate cells. Mol Cancer. 2008; 7: 25.

    OpenUrlCrossRefPubMed
50. 50.↵
    2. Nardinocchi L,
    3. Pantisano V,
    4. Puca R,
    5. Porru M,
    6. Aiello A,
    7. Grasselli A, et al.

    Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo. PLoS One. 2010; 5: e15048.
51. 51.↵
    2. Uzzo RG,
    3. Crispen PL,
    4. Golovine K,
    5. Makhov P,
    6. Horwitz EM,
    7. Kolenko VM.

    Diverse effects of zinc on NF-kappaB and AP-1 transcription factors: implications for prostate cancer progression. Carcinogenesis. 2006; 27: 1980–90.

    OpenUrlCrossRefPubMedWeb of Science
52. 52.↵
    2. Golovine K,
    3. Uzzo RG,
    4. Makhov P,
    5. Crispen PL,
    6. Kunkle D,
    7. Kolenko VM.

    Depletion of intracellular zinc increases expression of tumorigenic cytokines VEGF, IL-6 and IL-8 in prostate cancer cells via NF-kappaB-dependent pathway. Prostate. 2008; 68: 1443–9.

    OpenUrlCrossRefPubMedWeb of Science
53. 53.↵
    2. Ishii K,
    3. Usui S,
    4. Sugimura Y,
    5. Yoshida S,
    6. Hioki T,
    7. Tatematsu M, et al.

    Aminopeptidase n regulated by zinc in human prostate participates in tumor cell invasion. Int J Cancer. 2001; 92: 49–54.

    OpenUrlCrossRefPubMedWeb of Science
54. 54.↵
    2. Ishii K,
    3. Otsuka T,
    4. Iguchi K,
    5. Usui S,
    6. Yamamoto H,
    7. Sugimura Y, et al.

    Evidence that the prostate-specific antigen (PSA)/Zn²⁺ axis may play a role in human prostate cancer cell invasion. Cancer Lett. 2004; 207: 79–87.

    OpenUrlCrossRefPubMed
55. 55.↵
    2. Boissier S,
    3. Ferreras M,
    4. Peyruchaud O,
    5. Magnetto S,
    6. Ebetino FH,
    7. Colombel M, et al.

    Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res. 2000; 60: 2949–54.

    OpenUrlAbstract/FREE Full Text
56. 56.↵
    2. Wong PF,
    3. Abubakar S.

    Comparative transcriptional study of the effects of high intracellular zinc on prostate carcinoma cells. Oncol Rep. 2010; 23: 1501–16.

    OpenUrlPubMed
57. 57.↵
    2. Jouybari L,
    3. Kiani F,
    4. Akbari A,
    5. Sanagoo A,
    6. Sayehmiri F,
    7. Aaseth J, et al.

    A meta-analysis of zinc levels in breast cancer. J Trace Elem Med Biol. 2019; 56: 90–9.

    OpenUrl
58. 58.↵
    2. Woo W,
    3. Xu Z.

    Body zinc distribution profile during N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats at various levels of dietary zinc intake. Biol Trace Elem Res. 2002; 87: 157–69.

    OpenUrlCrossRefPubMedWeb of Science
59. 59.↵
    2. Lee R,
    3. Woo W,
    4. Wu B,
    5. Kummer A,
    6. Duminy H,
    7. Xu Z.

    Zinc accumulation in N-methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered expression of ZnT-1 and metallothionein. Exp Biol Med (Maywood). 2003; 228: 689–96.

    OpenUrlPubMedWeb of Science
60. 60.↵
    2. Lopez V,
    3. Foolad F,
    4. Kelleher SL.

    ZnT2-overexpression represses the cytotoxic effects of zinc hyper-accumulation in malignant metallothionein-null T47D breast tumor cells. Cancer Lett. 2011; 304: 41–51.

    OpenUrlCrossRefPubMed
61. 61.↵
    2. Perou CM,
    3. Sorlie T,
    4. Eisen MB,
    5. van de Rijn M,
    6. Jeffrey SS,
    7. Rees CA, et al.

    Molecular portraits of human breast tumours. Nature. 2000; 406: 747–52.

    OpenUrlCrossRefPubMedWeb of Science
62. 62.↵
    2. Yamashita S,
    3. Miyagi C,
    4. Fukada T,
    5. Kagara N,
    6. Che YS,
    7. Hirano T.

    Zinc transporter LIV1 controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature. 2004; 429: 298–302.

    OpenUrlCrossRefPubMedWeb of Science
63. 63.↵
    2. Taylor KM,
    3. Morgan HE,
    4. Smart K,
    5. Zahari NM,
    6. Pumford S,
    7. Ellis IO, et al.

    The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Mol Med. 2007; 13: 396–406.

    OpenUrlPubMedWeb of Science
64. 64.↵
    2. Hogstrand C,
    3. Kille P,
    4. Ackland ML,
    5. Hiscox S,
    6. Taylor KM.

    A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3). Biochem J. 2013; 455: 229–37.

    OpenUrlAbstract/FREE Full Text
65. 65.↵
    2. Kagara N,
    3. Tanaka N,
    4. Noguchi S,
    5. Hirano T.

    Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells. Cancer Sci. 2007; 98: 692–7.

    OpenUrlCrossRefPubMedWeb of Science
66. 66.↵
    2. Taylor KM,
    3. Muraina IA,
    4. Brethour D,
    5. Schmitt-Ulms G,
    6. Nimmanon T,
    7. Ziliotto S, et al.

    Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. Biochem J. 2016; 473: 2531–44.

    OpenUrlAbstract/FREE Full Text
67. 67.↵
    2. Taylor KM,
    3. Vichova P,
    4. Jordan N,
    5. Hiscox S,
    6. Hendley R,
    7. Nicholson RI.

    ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology. 2008; 149: 4912–20.

    OpenUrlCrossRefPubMedWeb of Science
68. 68.↵
    2. Taylor KM,
    3. Hiscox S,
    4. Nicholson RI,
    5. Hogstrand C,
    6. Kille P.

    Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Sci Signal. 2012; 5: ra11.

    OpenUrlAbstract/FREE Full Text
69. 69.↵
    2. Hogstrand C,
    3. Kille P,
    4. Nicholson RI,
    5. Taylor KM.

    Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol Med. 2009; 15: 101–11.

    OpenUrlCrossRefPubMedWeb of Science
70. 70.↵
    2. Bin BH,
    3. Bhin J,
    4. Seo J,
    5. Kim SY,
    6. Lee E,
    7. Park K, et al.

    Requirement of zinc transporter SLC39A7/ZIP7 for dermal development to fine-tune endoplasmic reticulum function by regulating protein disulfide isomerase. J Invest Dermatol. 2017; 137: 1682–91.

    OpenUrlCrossRefPubMed
71. 71.↵
    2. Ohashi W,
    3. Kimura S,
    4. Iwanaga T,
    5. Furusawa Y,
    6. Irie T,
    7. Izumi H, et al.

    Zinc transporter SLC39A7/ZIP7 promotes intestinal epithelial self-renewal by resolving ER stress. PLoS Genet. 2016; 12: e1006349.
72. 72.↵
    2. Thomas P,
    3. Converse A,
    4. Berg HA.

    ZIP9, a novel membrane androgen receptor and zinc transporter protein. Gen Comp Endocrinol. 2018; 257: 130–6.

    OpenUrl
73. 73.↵
    2. Yap X,
    3. Tan HY,
    4. Huang J,
    5. Lai Y,
    6. Yip GW,
    7. Tan PH, et al.

    Over-expression of metallothionein predicts chemoresistance in breast cancer. J Pathol. 2009; 217: 563–70.

    OpenUrlCrossRefPubMed
74. 74.↵
    2. Kim HG,
    3. Kim JY,
    4. Han EH,
    5. Hwang YP,
    6. Choi JH,
    7. Park BH, et al.

    Metallothionein-2A overexpression increases the expression of matrix metalloproteinase-9 and invasion of breast cancer cells. FEBS Lett. 2011; 585: 421–8.

    OpenUrlCrossRefPubMed
75. 75.↵
    2. Costello LC,
    3. Franklin RB.

    A review of the current status and concept of the emerging implications of zinc and zinc transporters in the development of pancreatic cancer. Pancreat Disord Ther. 2013; Suppl 4: 002.
76. 76.↵
    2. Costello LC,
    3. Levy BA,
    4. Desouki MM,
    5. Zou J,
    6. Bagasra O,
    7. Johnson LA, et al.

    Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma. Cancer Biol Ther. 2011; 12: 297–303.

    OpenUrlCrossRefPubMed
77. 77.↵
    2. Costello LC,
    3. Zou J,
    4. Desouki MM,
    5. Franklin RB.

    Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma. J Gastrointest Cancer. 2012; 43: 570–8.

    OpenUrl
78. 78.↵
    2. Li M,
    3. Zhang Y,
    4. Bharadwaj U,
    5. Zhai QJ,
    6. Ahern CH,
    7. Fisher WE, et al.

    Down-regulation of ZIP4 by RNA interference inhibits pancreatic cancer growth and increases the survival of nude mice with pancreatic cancer xenografts. Clin Cancer Res. 2009; 15: 5993–6001.

    OpenUrlAbstract/FREE Full Text
79. 79.↵
    2. Li M,
    3. Zhang Y,
    4. Liu Z,
    5. Bharadwaj U,
    6. Wang H,
    7. Wang X, et al.

    Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression. Proc Natl Acad Sci U S A. 2007; 104: 18636–41.

    OpenUrlAbstract/FREE Full Text
80. 80.↵
    2. Yang J,
    3. Zhang Y,
    4. Cui X,
    5. Yao W,
    6. Yu X,
    7. Cen P, et al.

    Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer. Curr Mol Med. 2013; 13: 401–9.

    OpenUrlPubMed
81. 81.↵
    2. Zhang Y,
    3. Bharadwaj U,
    4. Logsdon CD,
    5. Chen C,
    6. Yao Q,
    7. Li M.

    ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res. 2010; 16: 1423–30.

    OpenUrlAbstract/FREE Full Text
82. 82.
    2. Liu M,
    3. Yang J,
    4. Zhang Y,
    5. Zhou Z,
    6. Cui X,
    7. Zhang L, et al.

    ZIP4 promotes pancreatic cancer progression by repressing ZO-1 and Claudin-1 through a ZEB1-dependent transcriptional mechanism. Clin Cancer Res. 2018; 24: 3186–96.

    OpenUrlAbstract/FREE Full Text
83. 83.↵
    2. Jin H,
    3. Liu P,
    4. Wu Y,
    5. Meng X,
    6. Wu M,
    7. Han J, et al.

    Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer. Cancer Sci. 2018; 109: 2946–56.

    OpenUrl
84. 84.↵
    2. Cheng X,
    3. Wei L,
    4. Huang X,
    5. Zheng J,
    6. Shao M,
    7. Feng T, et al.

    Solute carrier family 39 member 6 gene promotes aggressiveness of esophageal carcinoma cells by increasing intracellular levels of zinc, activating phosphatidylinositol 3-kinase signaling, and up-regulating genes that regulate metastasis. Gastroenterology. 2017; 152: 1985–97.e12.

    OpenUrl
85. 85.↵
    2. Franklin RB,
    3. Levy BA,
    4. Zou J,
    5. Hanna N,
    6. Desouki MM,
    7. Bagasra O, et al.

    ZIP14 zinc transporter downregulation and zinc depletion in the development and progression of hepatocellular cancer. J Gastrointest Cancer. 2012; 43: 249–57.

    OpenUrlPubMed
86. 86.↵
    2. Costello LC,
    3. Franklin RB.

    The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship. Cancer Biol Ther. 2014; 15: 353–60.

    OpenUrlCrossRefPubMed
87. 87.↵
    2. Wang G,
    3. Biswas AK,
    4. Ma W,
    5. Kandpal M,
    6. Coker C,
    7. Grandgenett PM, et al.

    Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle. Nat Med. 2018; 24: 770–81.

    OpenUrlCrossRef
88. 88.↵
    2. Shakri AR,
    3. Zhong TJ,
    4. Ma W,
    5. Coker C,
    6. Kim S,
    7. Calluori S, et al.

    Upregulation of ZIP14 and altered zinc homeostasis in muscles in pancreatic cancer cachexia. Cancers. 2019; 12: 3.

    OpenUrl
89. 89.↵
    2. Xu X,
    3. Guo HJ,
    4. Xie HY,
    5. Li J,
    6. Zhuang RZ,
    7. Ling Q, et al.

    ZIP4, a novel determinant of tumor invasion in hepatocellular carcinoma, contributes to tumor recurrence after liver transplantation. Int J Biol Sci. 2014; 10: 245–56.

    OpenUrlCrossRefPubMed
90. 90.
    2. Gartmann L,
    3. Wex T,
    4. Grungreiff K,
    5. Reinhold D,
    6. Kalinski T,
    7. Malfertheiner P, et al.

    Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-an immunohistochemical study. J Trace Elem Med Biol. 2018; 49: 35–42.

    OpenUrl
91. 91.
    2. Li Q,
    3. Jin J,
    4. Liu J,
    5. Wang L,
    6. He Y.

    Knockdown of zinc transporter ZIP5 by RNA interference inhibits esophageal cancer growth in vivo. Oncol Res. 2016; 24: 205–14.

    OpenUrl
92. 92.
    2. Hashemian M,
    3. Hekmatdoost A,
    4. Poustchi H,
    5. Mohammadi Nasrabadi F,
    6. Abnet CC,
    7. Malekzadeh R.

    Systematic review of zinc biomarkers and esophageal cancer risk. Middle East J Dig Dis. 2014; 6: 177–85.

    OpenUrlPubMed
93. 93.
    2. Fan Q,
    3. Cai Q,
    4. Li P,
    5. Wang W,
    6. Wang J,
    7. Gerry E, et al.

    The novel ZIP4 regulation and its role in ovarian cancer. Oncotarget. 2017; 8: 90090–107.

    OpenUrl
94. 94.
    2. Wei Y,
    3. Dong J,
    4. Li F,
    5. Wei Z,
    6. Tian Y.

    Knockdown of SLC39A7 suppresses cell proliferation, migration and invasion in cervical cancer. EXCLI J. 2017; 16: 1165–76.

    OpenUrl
95. 95.
    2. Cunzhi H,
    3. Jiexian J,
    4. Xianwen Z,
    5. Jingang G,
    6. Shumin Z,
    7. Lili D.

    Serum and tissue levels of six trace elements and copper/zinc ratio in patients with cervical cancer and uterine myoma. Biol Trace Elem Res. 2003; 94: 113–22.

    OpenUrlCrossRefPubMedWeb of Science
96. 96.
    2. Pal D,
    3. Sharma U,
    4. Singh SK,
    5. Prasad R.

    Association between ZIP10 gene expression and tumor aggressiveness in renal cell carcinoma. Gene. 2014; 552: 195–8.

    OpenUrlCrossRefPubMed
97. 97.
    2. Dong X,
    3. Kong C,
    4. Zhang Z,
    5. Liu X,
    6. Zhan B,
    7. Chen Z, et al.

    hZIP1 that is down-regulated in clear cell renal cell carcinoma is negatively associated with the malignant potential of the tumor. Urol Oncol. 2014; 32: 885–92.

    OpenUrl
98. 98.
    2. Margalioth EJ,
    3. Schenker JG,
    4. Chevion M.

    Copper and zinc levels in normal and malignant tissues. Cancer. 1983; 52: 868–72.

    OpenUrlCrossRefPubMedWeb of Science
99. 99.
    2. Christudoss P,
    3. Selvakumar R,
    4. Fleming JJ,
    5. Mathew G.

    Zinc levels in paired normal and malignant human stomach and colon tissue. Biomedical Res. 2010; 21: 445–50.

    OpenUrl
100. 100.
     2. Boz A,
     3. Evliyaoglu O,
     4. Yildirim M,
     5. Erkan N,
     6. Karaca B.

     The value of serum zinc, copper, ceruloplasmin levels in patients with gastrointestinal tract cancers. Turk J Gastroenterol. 2005; 16: 81–4.

     OpenUrlPubMed
101. 101.
     2. Mulay IL,
     3. Roy R,
     4. Knox BE,
     5. Suhr NH,
     6. Delaney WE.

     Trace-metal analysis of cancerous and noncancerous human tissues. J Natl Cancer Inst. 1971; 47: 1–13.

     OpenUrlPubMedWeb of Science
102. 102.
     2. Diez M,
     3. Arroyo M,
     4. Cerdan FJ,
     5. Munoz M,
     6. Martin MA,
     7. Balibrea JL.

     Serum and tissue trace metal levels in lung cancer. Oncology. 1989; 46: 230–4.

     OpenUrlCrossRefPubMedWeb of Science
103. 103.
     2. Wu DM,
     3. Liu T,
     4. Deng SH,
     5. Han R,
     6. Xu Y.

     SLC39A4 expression is associated with enhanced cell migration, cisplatin resistance, and poor survival in non-small cell lung cancer. Sci Rep. 2017; 7: 7211.

     OpenUrl
104. 104.
     2. Wu L,
     3. Chaffee KG,
     4. Parker AS,
     5. Sicotte H,
     6. Petersen GM.

     Zinc transporter genes and urological cancers: integrated analysis suggests a role for ZIP11 in bladder cancer. Tumour Biol. 2015; 36: 7431–7.

     OpenUrl
105. 105.
     2. Liu Y,
     3. Liu T,
     4. Jin H,
     5. Yin L,
     6. Yu H,
     7. Bi J.

     MiR-411 suppresses the development of bladder cancer by regulating ZnT1. Onco Targets Ther. 2018; 11: 8695–704.

     OpenUrl
106. 106.
     2. Ishida S,
     3. Kasamatsu A,
     4. Endo-Sakamoto Y,
     5. Nakashima D,
     6. Koide N,
     7. Takahara T, et al.

     Novel mechanism of aberrant ZIP4 expression with zinc supplementation in oral tumorigenesis. Biochem Biophys Res Commun. 2017; 483: 339–45.

     OpenUrl
107. 107.
     2. Bay B,
     3. Chan Y,
     4. Fong C,
     5. Leong H.

     Differential cellular zinc levels in metastatic and primary nasopharyngeal carcinoma. Int J Oncol. 1997; 11: 745–8.

     OpenUrlPubMed
108. 108.↵
     2. Zeng Q,
     3. Liu YM,
     4. Liu J,
     5. Han J,
     6. Guo JX,
     7. Lu S, et al.

     Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells. Cell Death Dis. 2019; 10: 588.

     OpenUrl
109. 109.↵
     2. Jayaraman AK,
     3. Jayaraman S.

     Increased level of exogenous zinc induces cytotoxicity and up-regulates the expression of the ZnT-1 zinc transporter gene in pancreatic cancer cells. J Nutr Biochem. 2011; 22: 79–88.

     OpenUrlCrossRefPubMed
110. 110.↵
     2. Donadelli M,
     3. Dalla Pozza E,
     4. Scupoli MT,
     5. Costanzo C,
     6. Scarpa A,
     7. Palmieri M.

     Intracellular zinc increase inhibits p53(-/-) pancreatic adenocarcinoma cell growth by ROS/AIF-mediated apoptosis. Biochim Biophys Acta. 2009; 1793: 273–80.

     OpenUrlCrossRefPubMedWeb of Science
111. 111.↵
     2. Fong LY,
     3. Nguyen VT,
     4. Farber JL.

     Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc. J Natl Cancer Inst. 2001; 93: 1525–33.

     OpenUrlCrossRefPubMedWeb of Science
112. 112.↵
     2. Sun J,
     3. Liu J,
     4. Pan X,
     5. Quimby D,
     6. Zanesi N,
     7. Druck T, et al.

     Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains. Carcinogenesis. 2011; 32: 351–8.

     OpenUrlPubMed
113. 113.↵
     2. Dani V,
     3. Goel A,
     4. Vaiphei K,
     5. Dhawan DK.

     Chemopreventive potential of zinc in experimentally induced colon carcinogenesis. Toxicol Lett. 2007; 171: 10–8.

     OpenUrlCrossRefPubMedWeb of Science
114. 114.↵
     2. Lin YS,
     3. Lin LC,
     4. Lin SW.

     Effects of zinc supplementation on the survival of patients who received concomitant chemotherapy and radiotherapy for advanced nasopharyngeal carcinoma: follow-up of a double-blind randomized study with subgroup analysis. Laryngoscope. 2009; 119: 1348–52.

     OpenUrlCrossRefPubMedWeb of Science
115. 115.↵
     2. Ghosh SK,
     3. Kim P,
     4. Zhang XA,
     5. Yun SH,
     6. Moore A,
     7. Lippard SJ, et al.

     A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing. Cancer Res. 2010; 70: 6119–27.

     OpenUrlAbstract/FREE Full Text
116. 116.↵
     2. Golovine K,
     3. Makhov P,
     4. Uzzo RG,
     5. Shaw T,
     6. Kunkle D,
     7. Kolenko VM.

     Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo. Clin Cancer Res. 2008; 14: 5376–84.

     OpenUrlAbstract/FREE Full Text
117. 117.↵
     2. Feng P,
     3. Li TL,
     4. Guan ZX,
     5. Franklin RB,
     6. Costello LC.

     Effect of zinc on prostatic tumorigenicity in nude mice. Ann N Y Acad Sci. 2003; 1010: 316–20.

     OpenUrlCrossRefPubMedWeb of Science
118. 118.↵
     2. Prasad AS,
     3. Mukhtar H,
     4. Beck FW,
     5. Adhami VM,
     6. Siddiqui IA,
     7. Din M, et al.

     Dietary zinc and prostate cancer in the tramp mouse model. J Med Food. 2010; 13: 70–6.

     OpenUrlCrossRefPubMed
119. 119.↵
     2. Shah MR,
     3. Kriedt CL,
     4. Lents NH,
     5. Hoyer MK,
     6. Jamaluddin N,
     7. Klein C, et al.

     Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer. J Exp Clin Cancer Res. 2009; 28: 84.

     OpenUrlCrossRefPubMed
120. 120.↵
     2. Ko YH,
     3. Woo YJ,
     4. Kim JW,
     5. Choi H,
     6. Kang SH,
     7. Lee JG, et al.

     High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction model. Asian J Androl. 2010; 12: 164–70.

     OpenUrlPubMed
121. 121.↵
     2. Dhawan DK,
     3. Chadha VD.

     Zinc: a promising agent in dietary chemoprevention of cancer. Indian J Med Res. 2010; 132: 676–82.

     OpenUrlPubMed
122. 122.↵
     2. Sussman D,
     3. Smith LM,
     4. Anderson ME,
     5. Duniho S,
     6. Hunter JH,
     7. Kostner H, et al.

     SGN-LIV1A: a novel antibody-drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer. Mol Cancer Ther. 2014; 13: 2991–3000.

     OpenUrlAbstract/FREE Full Text
123. 123.↵
     2. Nolin E,
     3. Gans S,
     4. Llamas L,
     5. Bandyopadhyay S,
     6. Brittain SM,
     7. Bernasconi-Elias P, et al.

     Discovery of a ZIP7 inhibitor from a notch pathway screen. Nat Chem Biol. 2019; 15: 179–88.

     OpenUrl
124. 124.↵
     2. Chabosseau P,
     3. Woodier J,
     4. Cheung R,
     5. Rutter GA.

     Sensors for measuring subcellular zinc pools. Metallomics. 2018; 10: 229–39.

     OpenUrl
125. 125.↵
     2. Chabosseau P,
     3. Tuncay E,
     4. Meur G,
     5. Bellomo EA,
     6. Hessels A,
     7. Hughes S, et al.

     Mitochondrial and ER-targeted eCALWY probes reveal high levels of free Zn²⁺. ACS Chem Biol. 2014; 9: 2111–20.

     OpenUrlCrossRefPubMed