| SLC39A7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SLC39A7, D6S115E, D6S2244E, H2-KE4, HKE4, KE4, RING5, ZIP7, solute carrier family 39 member 7, AGM9 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 601416 MGI: 95909 HomoloGene: 5072 GeneCards: SLC39A7 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Zinc transporter SLC39A7 (ZIP7), also known as solute carrier family 39 member 7, is a protein that in humans is encoded by the SLC39A7 gene.[5][6][7] Its fruit fly orthologue is Catsup.
Function[edit]
Zinc is an essential cofactor for more than 50 classes of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. Zinc cannot passively diffuse across cell membranes and requires specific transporters, such as SLC39A7, to enter the cytosol from both the extracellular environment and from intracellular storage compartments.[7]
ZIP7 is a membrane transport protein of the endoplasmic reticulum.[8] Phosphorylation of ZIP7 by casein kinase 2 stimulates the release of zinc ions from the endoplasmic reticulum[9] This provides a signal transduction pathway by which activation of cell surface receptors such as the epidermal growth factor receptor can regulate the activity of downstream phosphatases and kinases.
Role in Cancer[edit]
ZIP7, a member of the solute carrier family 39 (SLC39) of zinc transporters, emerges as a pivotal factor in cancer progression across multiple malignancies. In breast cancer, ZIP7 expression is markedly elevated in primary tumors, particularly in basal and Her2 subtypes, and correlates with advanced disease stage, metastasis, recurrence, and poorer prognosis. Notably, its hyperactivation is implicated in endocrine resistance, suggesting a crucial role in Endocrine therapy resistance mechanisms.[10][11]
In colorectal cancer, ZIP7 upregulation is observed in tumor tissues compared to normal counterparts. Inhibition of ZIP7 leads to suppressed cell proliferation, colony formation, and enhanced apoptosis, while its heightened presence correlates with adverse patient outcomes, highlighting its significance as a potential prognostic marker.[12][13] Similarly, ZIP7 exhibits elevated expression in cervical cancer tissues, where its knockdown results in inhibited proliferation, migration, and invasion of cancer cells. Furthermore, modulation of epithelial-mesenchymal transition markers underscores ZIP7's involvement in metastatic processes, suggesting its potential as a therapeutic target to impede disease progression.[14] In hepatocellular carcinoma, specific inhibition of ZIP7 attenuates PI3K/AKT signaling, leading to suppressed cell growth, colony formation, migration, invasion, and enhanced apoptosis both in vitro and in vivo. This underscores ZIP7's critical role in hepatocellular carcinoma tumorigenesis and its potential as a therapeutic target in this malignancy.[15]
Moreover, microRNAs play a regulatory role in ZIP7 expression across different cancer types. For instance, in prostate cancer, miR-15a-3p targets ZIP7, leading to the suppression of the Wnt/β-catenin signaling pathway and inhibition of proliferation, invasion, and epithelial-mesenchymal transition. Similarly, in gastric cancer, miR-139-5p negatively regulates ZIP7, inhibiting ZIP7-mediated activation of the Akt/mTOR pathway, thereby suppressing cell proliferation and migration while promoting apoptosis.[16][17]
In a study presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, researchers introduced rabbit polyclonal antibodies specifically targeting ZIP7 to both human triple-negative breast cancer cells (TNBC) and normal breast epithelial cells (NBE) obtained from the same patient. Utilizing flow cytometry analysis, they observed substantial binding of the ZIP7 antibodies to TNBC cells, while minimal binding was noted in NBE cells from the same individual. Moreover, cytotoxicity assays revealed that the ZIP7-targeted antibodies, in combination with a secondary anti-rabbit Antibody-Drug Conjugate (ADC), selectively induced cell death in TNBC cells over NBE cells. Importantly, this preferential killing effect was attributed to the aberrant surface expression of ZIP7 on TNBC cells, coupled with its involvement in cell proliferation-related signaling pathways specific to TNBC.[18]
In summary, ZIP7 emerges as a critical regulator of cancer progression, influencing key cellular processes such as proliferation, invasion, migration, and apoptosis across various malignancies. Targeting ZIP7 or its regulatory mechanisms holds therapeutic promise in cancer treatment strategies, highlighting its potential as a prognostic marker and therapeutic target in oncology research.
See also[edit]
References[edit]
- ^ a b c ENSG00000229802, ENSG00000226614, ENSG00000112473, ENSG00000206288, ENSG00000224399 GRCh38: Ensembl release 89: ENSG00000227402, ENSG00000229802, ENSG00000226614, ENSG00000112473, ENSG00000206288, ENSG00000224399 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024327 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Ando A, Kikuti YY, Shigenari A, Kawata H, Okamoto N, Shiina T, Chen L, Ikemura T, Abe K, Kimura M, Inoko H (Dec 1996). "cDNA cloning of the human homologues of the mouse Ke4 and Ke6 genes at the centromeric end of the human MHC region". Genomics. 35 (3): 600–2. doi:10.1006/geno.1996.0405. PMID 8812499.
- ^ Hanson IM, Trowsdale J (Aug 1991). "Colinearity of novel genes in the class II regions of the MHC in mouse and human". Immunogenetics. 34 (1): 5–11. doi:10.1007/BF00212306. PMID 1855816. S2CID 30046348.
- ^ a b "Entrez Gene: SLC39A7 solute carrier family 39 (zinc transporter), member 7".
- ^ Taylor KM, Morgan HE, Johnson A, Nicholson RI (2004). "Structure‒function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters". Biochemical Journal. 377 (Pt 1): 131–139. doi:10.1042/BJ20031183. PMC 1223853. PMID 14525538.
- ^ Taylor KM, Kille P, Hogstrand C (2012). "Protein kinase CK2 opens the gate for zinc signaling". Cell Cycle. 11 (10): 1863–1864. doi:10.4161/cc.20414. PMC 3359116. PMID 22580452.
- ^ Liu, Limei; Yang, Jiaomin; Wang, Chao (28 August 2020). "Analysis of the prognostic significance of solute carrier (SLC) family 39 genes in breast cancer". Bioscience Reports. 40 (8). doi:10.1042/BSR20200764. PMC 7426635. PMID 32744318.
- ^ Samuel, Jones; Georgia, Farr; Thirayost, Nimmanon; Silvia, Ziliotto; Julia M.W., Gee; Kathryn M., Taylor (26 April 2022). "The importance of targeting signalling mechanisms of the SLC39A family of zinc transporters to inhibit endocrine resistant breast cancer". Exploration of Targeted Anti-tumor Therapy: 224–239. doi:10.37349/etat.2022.00080. PMC 7612740.
- ^ Sheng, Nengquan; Yan, Li; You, Weiqiang; Tan, Gewen; Gong, Jianfeng; Chen, Hongqi; Yang, Yi; Hu, Landian; Wang, Zhigang (1 October 2017). "Knockdown of SLC39A7 inhibits cell growth and induces apoptosis in human colorectal cancer cells". Acta Biochimica et Biophysica Sinica. 49 (10): 926–934. doi:10.1093/abbs/gmx094.
- ^ Luo, Yang; Shen, Yicheng; Ju, Zhong; Zhang, Zhi (October 2020). "ZIP7 (SLC39A7) expression in colorectal cancer and its correlation with clinical prognosis". Translational Cancer Research. 9 (10): 6471–6478. doi:10.21037/tcr-20-2640. PMC 8798949. PMID 35117255.
- ^ Wei, Yongqing; Dong, Jie; Li, Fuli; Wei, Zhuqing; Tian, Yuling (2017). "Knockdown of SLC39A7 suppresses cell proliferation, migration and invasion in cervical cancer". EXCLI Journal; 16:Doc1165; ISSN 1611-2156. doi:10.17179/excli2017-690.
- ^ Tong, Qing; Yan, Dong; Cao, Yan; Dong, Xiaogang; Abula, Yimamumaimaitijiang; Yang, Huan; Kong, Panpan; Yi, Mingyu (21 July 2023). "NVS-ZP7-4 inhibits hepatocellular carcinoma tumorigenesis and promotes apoptosis via PI3K/AKT signaling". Scientific Reports. 13 (1): 11795. Bibcode:2023NatSR..1311795T. doi:10.1038/s41598-023-38596-7. PMC 10362011. PMID 37479837.
- ^ Cui, Yu; Yang, Yi; Ren, Liang; Yang, Jun; Wang, Bin; Xing, Tianjun; Chen, Huiqing; Chen, Mingxiao (1 September 2019). "miR-15a-3p Suppresses Prostate Cancer Cell Proliferation and Invasion by Targeting SLC39A7 Via Downregulating Wnt/β-Catenin Signaling Pathway". Cancer Biotherapy and Radiopharmaceuticals. 34 (7): 472–479. doi:10.1089/cbr.2018.2722. PMID 31135177.
- ^ Zhang, Yanting; Bai, Jie; Si, Wangli; Yuan, Shanshan; Li, Yijun; Chen, Xiaolu (28 February 2020). "SLC39A7, regulated by miR-139-5p, induces cell proliferation, migration and inhibits apoptosis in gastric cancer via Akt/mTOR signaling pathway". Bioscience Reports. 40 (2). doi:10.1042/BSR20200041. PMC 7048674. PMID 32109290.
- ^ Manavalan, John Sanil; Mor, Danielle; Davis, Joseph; Saini, Sharanjot; Pal, Ipsita; Feith, David; Hikichi, Yuichi; Davis, Elliot (22 March 2024). "Abstract 4109: Discovery of a novel cancer-specific antigen for therapeutic targeting using the Oncotope platform". Cancer Research. 84 (6_Supplement): 4109. doi:10.1158/1538-7445.AM2024-4109.
Further reading[edit]
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Taylor KM, Morgan HE, Johnson A, et al. (2003). "Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters". Biochem. J. 375 (Pt 1): 51–9. doi:10.1042/BJ20030478. PMC 1223660. PMID 12839489.
- Taylor KM, Morgan HE, Johnson A, Nicholson RI (2004). "Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters". Biochem. J. 377 (Pt 1): 131–9. doi:10.1042/BJ20031183. PMC 1223853. PMID 14525538.
- Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. Bibcode:2003Natur.425..805M. doi:10.1038/nature02055. PMID 14574404.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Huang L, Kirschke CP, Zhang Y, Yu YY (2005). "The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus". J. Biol. Chem. 280 (15): 15456–63. doi:10.1074/jbc.M412188200. PMID 15705588.
- Kim JE, Tannenbaum SR, White FM (2005). "Global phosphoproteome of HT-29 human colon adenocarcinoma cells". J. Proteome Res. 4 (4): 1339–46. doi:10.1021/pr050048h. PMID 16083285.
- Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.