ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM

Overview

Journal Mol Cancer Res

Specialty Cell Biology

Date 2015 May 22

PMID 25995384

Citations 22

Authors

Xue-Song Liu

Matthew D Genet

Jenna E Haines

Elie K Mehanna

Shaowei Wu

Hung-I Harry Chen

Yidong Chen

Abrar A Qureshi

Jiali Han

Xiang Chen

David E Fisher

Pier Paolo Pandolfi

Zhi-Min Yuan

Affiliations

Soon will be listed here.

Abstract

Unlabelled: The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated downregulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens.

Implications: Together, these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications.

Citing Articles

U3 snoRNA-mediated degradation of ZBTB7A regulates aerobic glycolysis in isocitrate dehydrogenase 1 wild-type glioblastoma cells.

Dong W, Liu Y, Wang P, Ruan X, Liu L, Xue Y CNS Neurosci Ther. 2023; 29(10):2811-2825.

PMID: 37066523 PMC: 10493654. DOI: 10.1111/cns.14218.

Identification and Characterization of Metabolic Subtypes of Endometrial Cancer Using a Systems-Level Approach.

Srivastava A, Vinod P Metabolites. 2023; 13(3).

PMID: 36984849 PMC: 10054278. DOI: 10.3390/metabo13030409.

ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression.

Liu J, Chou Z, Li C, Huang K, Wang X, Li X Cancer Cell Int. 2022; 22(1):179.

PMID: 35501800 PMC: 9063087. DOI: 10.1186/s12935-022-02596-w.

Role of ZBTB7A zinc finger in tumorigenesis and metastasis.

Singh A, Verma S, Kushwaha P, Prajapati K, Shuaib M, Kumar S Mol Biol Rep. 2021; 48(5):4703-4719.

PMID: 34014468 DOI: 10.1007/s11033-021-06405-x.

Capsaicin Inhibits Proliferation and Induces Apoptosis in Breast Cancer by Down-Regulating FBI-1-Mediated NF-κB Pathway.

Chen M, Xiao C, Jiang W, Yang W, Qin Q, Tan Q Drug Des Devel Ther. 2021; 15:125-140.

PMID: 33469265 PMC: 7811378. DOI: 10.2147/DDDT.S269901.

References

Sers C, Riethmuller G, Johnson J . MUC18, a melanoma-progression associated molecule, and its potential role in tumor vascularization and hematogenous spread. Cancer Res. 1994; 54(21):5689-94. View

Xie S, Luca M, Huang S, Gutman M, Reich R, Johnson J . Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 1997; 57(11):2295-303. View

Pessler F, Pendergrast P, Hernandez N . Purification and characterization of FBI-1, a cellular factor that binds to the human immunodeficiency virus type 1 inducer of short transcripts. Mol Cell Biol. 1997; 17(7):3786-98. PMC: 232230. DOI: 10.1128/MCB.17.7.3786. View

Kukita A, Kukita T, Ouchida M, Maeda H, Yatsuki H, Kohashi O . Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis. Blood. 1999; 94(6):1987-97. View

Liu C, Prazak L, Fajardo M, Yu S, Tyagi N, Di Cesare P . Leukemia/lymphoma-related factor, a POZ domain-containing transcriptional repressor, interacts with histone deacetylase-1 and inhibits cartilage oligomeric matrix protein gene expression and chondrogenesis. J Biol Chem. 2004; 279(45):47081-91. DOI: 10.1074/jbc.M405288200. View

Maeda T, Hobbs R, Merghoub T, Guernah I, Zelent A, Cordon-Cardo C . Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature. 2005; 433(7023):278-85. DOI: 10.1038/nature03203. View

Pacifico M, Grover R, Richman P, Daley F, Buffa F, Wilson G . Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker. Plast Reconstr Surg. 2005; 115(2):367-75. DOI: 10.1097/01.prs.0000148417.86768.c9. View

Talantov D, Mazumder A, Yu J, Briggs T, Jiang Y, Backus J . Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res. 2005; 11(20):7234-42. DOI: 10.1158/1078-0432.CCR-05-0683. View

Melnikova V, Bar-Eli M . Bioimmunotherapy for melanoma using fully human antibodies targeting MCAM/MUC18 and IL-8. Pigment Cell Res. 2006; 19(5):395-405. DOI: 10.1111/j.1600-0749.2006.00331.x. View

10.

Kelly K, Daniel J . POZ for effect--POZ-ZF transcription factors in cancer and development. Trends Cell Biol. 2006; 16(11):578-87. DOI: 10.1016/j.tcb.2006.09.003. View

11.

Zack T, Schumacher S, Carter S, Cherniack A, Saksena G, Tabak B . Pan-cancer patterns of somatic copy number alteration. Nat Genet. 2013; 45(10):1134-40. PMC: 3966983. DOI: 10.1038/ng.2760. View

12.

Chin L . The genetics of malignant melanoma: lessons from mouse and man. Nat Rev Cancer. 2003; 3(8):559-70. DOI: 10.1038/nrc1145. View

13.

Futreal P, Coin L, Marshall M, Down T, Hubbard T, Wooster R . A census of human cancer genes. Nat Rev Cancer. 2004; 4(3):177-83. PMC: 2665285. DOI: 10.1038/nrc1299. View

14.

Lehmann J, Holzmann B, Breitbart E, Schmiegelow P, Riethmuller G, Johnson J . Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. Cancer Res. 1987; 47(3):841-5. View

15.

Chen Z, Brand N, Chen A, Chen S, Tong J, Wang Z . Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993; 12(3):1161-7. PMC: 413318. DOI: 10.1002/j.1460-2075.1993.tb05757.x. View

16.

Luca M, Hunt B, Bucana C, Johnson J, Fidler I, Bar-Eli M . Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. Melanoma Res. 1993; 3(1):35-41. DOI: 10.1097/00008390-199304000-00006. View

17.

Shih I, Elder D, Speicher D, Johnson J, Herlyn M . Isolation and functional characterization of the A32 melanoma-associated antigen. Cancer Res. 1994; 54(9):2514-20. View

18.

Nguyen D, Massague J . Genetic determinants of cancer metastasis. Nat Rev Genet. 2007; 8(5):341-52. DOI: 10.1038/nrg2101. View

19.

Maeda T, Merghoub T, Hobbs R, Dong L, Maeda M, Zakrzewski J . Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science. 2007; 316(5826):860-6. PMC: 2978506. DOI: 10.1126/science.1140881. View

20.

Costoya J . Functional analysis of the role of POK transcriptional repressors. Brief Funct Genomic Proteomic. 2007; 6(1):8-18. DOI: 10.1093/bfgp/elm002. View