Background
Structure and classification
MT isoforms | Gene ID | Location | GenBank accession number | References |
---|---|---|---|---|
MT1A | 4489 | Chromosome 16, NC_000016.10 (56638666..56640087) | NM_005946.2 | |
MT1B | 4490 | Chromosome 16, NC_000016.10 (56651899..56653204) | NM_005947.2 | |
MT1E | 4493 | Chromosome 16, NC_000016.10 (56625673..56627112) | NM_175617.3 | |
MT1F | 4494 | Chromosome 16, NC_000016.10 (56657943..56659303) | NM_005949.3 | |
MT1G | 4495 | Chromosome 16, NC_000016.10 (56666735..56668065, complement) | NM_005950.2 | |
MT1H | 4496 | Chromosome 16, NC_000016.10 (56669814..56671129) | NM_005951.2 | |
MT1M | 4499 | Chromosome 16, NC_000016.10 (56632622..56633986) | NM_176870.2 | |
MT1X | 4501 | Chromosome 16, NC_000016.10 (56682470..56684196) | NM_005952.3 | |
MT2A | 4502 | Chromosome 16, NC_000016.10 (56608566..56609497) | NM_005953.4 | |
MT3 | 4504 | Chromosome 16, NC_000016.10 (56589355..56591088) | NM_005954.3 | |
MT4 | 84560 | Chromosome 16, NC_000016.10 (56565049..56568957) | NM_032935.2 |
Roles of MTs in cancer
Cancer type | MT isoforms | Expression | Functions | References |
---|---|---|---|---|
Acute nonlymphoblastic leukemia | MT | Positive | Resistance-related proteins | [182] |
Acute myeloid leukemia | MT1G, MT1A | Positive | Inversely correlated with PU.1 expression | [183] |
MT3 | Down | Promoter hypermethylation | [154] | |
Adenoid cystic carcinomas of the salivary glands | MT | Up | Myoepithelial differentiation | [184] |
Basal cell carcinoma | MT | Up | Infiltrative growth | [185] |
MT1, MT2 | Up | Promote proliferation: Ki-67 antigen expression | [43] | |
MT3 | Down | Possibly based on DNA methylation | [186] | |
MT3 | Low to moderate expression | Carcinogenesis | [187] | |
Bladder carcinoma | MT | Up | Drug resistance | [188] |
MT2 | Up | Cisplatin resistance | [99] | |
MT3 | Up | Carcinogenesis and increase tumor grade | [189] | |
MT1X | Up | Correlated with tumor grade | [190] | |
MT | Up | Poor survival and cisplatin resistance | [23] | |
Breast cancer | MT3 | Up | Poor prognosis | [130] |
MT2A | Up | Increase invasiveness | [191] | |
MT1E | Present in estrogen receptor (ER)-negative breast cancer | Myoepithelial differentiation and tumor invasiveness | [191] | |
MT2A | Up | Modulate cell cycle via the ATM/Chk2/cdc25A signaling pathway | [39] | |
MT2A | Up | Upregulation of matrix metalloproteinase (MMP)-9; enhance cell invasion and migration | [82] | |
MT3 | Up | Increase invasiveness | [83] | |
Cholangiocarcinoma | MT | Partly positive | Poor prognosis | [128] |
Colonic cancer | MT | Up | Promote proliferation | [36] |
MT1F | Down | Loss of heterozygosity | [52] | |
MT1G, MT1X, MT2A | Down | Associated with the depth of tumor invasion, lymph node metastasis, and tumor stage | [52] | |
Colorectal cancer | MT2A, MT1B, MT1F, MT1G, MT1H, MT1B, MT1F, MT1G, MT1H, MT2A | Down | Poor clinical outcome | [192] |
MT1E, MT1F, MT1G, MT1H, MT1M, MT1X MT2A | Down | Epigenetic mechanisms | [6] | |
MT2A | Up | Interact with Fas-associated death domain (FADD) in NF-κB pathway to promote cell proliferation | [49] | |
MT1G | Down | Colorectal cancer cell differentiation | [67] | |
Ductal breast cancer | MT1E | High in ER-negative cancer tissues | Mediate effector genes downstream of ER | [193] |
MT1F | Up | Influence histological differentiation | [58] | |
MT2A | Up | Cell proliferation | [41] | |
MT2A | Up | Chemoresistance (doxorubicin) | [59] | |
MT1, MT2 | Up | Increased proliferative potential | [20] | |
MT3 | Down | Epigenetic changes | [88] | |
Endometrial carcinoma | MT1, MT2 | Up | Modify p53 expression | [141] |
MT1E | Down | Promoter hypermethylation | [143] | |
Esophageal adenocarcinoma | MT3 | Down | DNA methylation | [152] |
Esophageal squamous cell carcinoma | MT | Up | Chemoresistance to cisplatin; poor prognosis | [194] |
MT3 | Down | DNA methylation | [153] | |
MT1G | Down | Gene methylation | [145] | |
MT1G | Down | Promoter hypermethylation | [146] | |
MT1M | Down | DNA methylation; correlated with smoking duration | [195] | |
Gallbladder carcinoma | MT | Up | Histological dedifferentiation | [63] |
Gastric carcinoma | MT3 | Down | Hypermethylation | [151] |
MT1G | Up | Cisplatin resistance | [196] | |
MT1X | Up | Irinotecan resistance | [103] | |
MT | Up | Poor survival and high recurrence rate | [81] | |
MT2A | Down | Inhibit the activation of the NF-κB pathway | [135] | |
MT2A | Down | Be a potential target of miR-23a | [197] | |
MT1D (MTM) | Down | Enhance migration and invasion | [198] | |
MT1M, MT1JP | Down | Associated with tumor diameter, differentiation, lymphatic metastasis, distal metastasis, invasion, and tumor node metastasis (TNM) stage | [199] | |
Glioma | MT1E | In proportion to the motility of glioma cell | Enhance tumor proliferation, invasion, and migration through regulation of activation and expression of MMPs | |
Hepatoblastoma | MT1G | Down | Promoter hypermethylation | [147] |
Hepatocellular carcinoma | MT1F | Down | Cell growth | [200] |
MT1G | Down | Allelic loss on chromosome 16q12.1-q23.1 | [155] | |
MT1, MT2A | Down | Transcriptional repression: dephosphorylation of the transcription factor CCAAT/enhancer-binding protein (C/EBP) α through phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway | [25] | |
MT1X, MT2A | Down | Malignant transformation of hepatocytes; local invasion; hepatitis B virus infection | [201] | |
MT1G | Down | Tumor suppressor gene; promoter hypermethylation | [148] | |
MT1M | Down | Increase NF-κB activity | [142] | |
MT1, MT2 | Down | Promoter hypermethylation and transcriptional repression; prognostic marker | [133] | |
MT1M, MT1G | Down | Promoter methylation | [136] | |
MT1M | Down | Poor prognosis | [134] | |
MT1, MT2 | Down | Associated with the disruption of circadian clock genes | [202] | |
MT1H | Down | Regulate the Wnt/β-catenin signaling pathway | [8] | |
MT1M | Down | Inhibit tumorigenesis | [203] | |
Intrahepatic cholangiocarcinoma | MT1A, MT1E, MT1F, MT1G, MT1H, MT1IP, MT1X | Down | Hypermethylation | [204] |
Lung cancer | MT1A, MT2A, MT1E, MT1G | Down | Gene methylation | [205] |
Large cell lung cancer | MT1F, MT1G, MT1M, MT1X | Up | Poor prognosis | [206] |
Melanoma | MT | Up | Poor prognosis | |
MT1E | Down | DNA methylation | [144] | |
MT1, MT2 | Up | Intratumoural macrophage infiltration to defect host immune response and metastasis formation | [77] | |
Nasopharyngeal cancer | MT | Up | Cell proliferation | [21] |
Non-small cell lung cancer | MT | Up | Tumor cell proliferation and short survival | [122] |
MT1H | Up | Drug resistance (cisplatin) | [207] | |
MT1, MT2 | Up | Promote proliferation: expressions of Ki-67 and minichromosome maintenance protein-2 (MCM-2) (positive correlation) | [40] | |
MT3 | Up | Pathogenesis | [208] | |
MT1B, MT1F, MT1G, MT1H, MT1X | Up | Pathogenesis | [131] | |
MT1F, MT2A | Up | Poor outcome | [131] | |
MT1E | Down | Cell differentiation | [131] | |
Oral squamous cell carcinoma | MT | Up | Poor prognosis | [127] |
MT1A, MT1X, MT3, MT4 | Down | Possible markers for oral carcinogenesis | [209] | |
MT1G | Down | Poor survival | [209] | |
MT1F | Up | Associated with tobacco use | [209] | |
Osteosarcoma | MT1E, MT1H, MT1X, MT2A, MT1B, MT1G, MT1L | Up | Drug resistance | [210] |
Ovarian cancer | MT1, MT2 | Up | Mutant p53; histological grade | [22] |
MT2A | Up | Inhibit cell death | [211] | |
MT1L, MT1X, MT2A | Up | Low malignant potential or early cancer onset | [212] | |
Pancreatic carcinoma | MT | Partly positive | Metastasis, poor prognosis, and poor histological grade | [62] |
Papillary thyroid carcinoma | MT1G | Down | Promoter hypermethylation | [149] |
MT1E, MT1G, MT1X, MT2A | Down | Promoter methylation and transcriptional repression | [7] | |
MT1G | Down | Modulate the activity of the PI3K/AKT and Rb/E2F pathways | [89] | |
Prostate cancer | MT3 | Highly variable increase | Control prostate epithelial cell growth | [213] |
MT1X | Down | Advanced prostate cancer | [214] | |
MT2A | Up | Inhibit cell death | [211] | |
MT3 | Up | Inhibit cell growth and increase drug resistance | [53] | |
MT1G | Down | Promoter hypermethylation | [150] | |
MT1F, MT1M | Down | Associated with perineural invasion | [215] | |
MT1H | Down | Enhance the histone methyltransferase activity of euchromatin histone methyltransferase 1 (EHMT1) | [26] | |
MT2A | Down | Single nucleotide polymorphism (SNP); metal accumulation | [14] | |
MT3 | Depend on cell type | Increase cell proliferation, invasion, and tumorigenic activities | [104] | |
MT1E | Down | DNA methylation | [10] | |
Renal cell cancer | MT | Up | Tumor grade | [64] |
MT2A | Up | Stimulate cellular proliferation | [216] | |
MT1A, MT1G | Down | Growth arrest and induction of apoptosis | [216] | |
MT1A, MT1E, MT1G, MT1H, MT1L | Down | Tumorigenesis | [217] | |
MT1H, MT1G, MT2A | Down | Promoter methylation | [45] | |
Salivary gland adenocarcinoma | MT | Up | High immunoreactivity and microenvironment remodeling | [90] |
Serous ovarian cancer | MT | Up | Diagnosis of malignancy and worse prognosis | [218] |
Small cell lung cancer | MT | 45% positive | P53 expression and short-term survival | [121] |
Soft tissue sarcoma | MT | Up | Ki-67 expression, grade of malignancy, and prognostic appraisal | [44] |
MT2A, MT1X, MT1F, MT1H | Up | Metastasis | [219] | |
Squamous cell carcinoma of the tongue | MT | Positive | Delay cells entering apoptosis | [220] |
MT | Positive | Correlated with depth of invasion, vascular invasion, and lymph node metastasis | [221] | |
Testicular cancer | MT | Up | Chemoresistance | [222] |
MT | Up | Early diagnosis | [115] | |
Transitional cell carcinoma of the bladder | MT | Up | Poor survival | [126] |
Expression of MT isoforms in various types of cancers
Tumorigenesis
Tumor growth
Tumor differentiation
Tumor angiogenesis
Tumor metastasis
Tumor microenvironment remodeling and immune escape
Tumor drug resistance
MTs as biomarkers for cancer diagnosis and prognosis
Mechanisms involving MTs in cancer
MT isoforms | Mechanisms | References |
---|---|---|
MTs | Regulation of P53 activity | |
MTs | Regulation of NF-κB activity | |
MTs | Methylation of DNA promoters | |
MT1H | Increasing the methyltransferase activity of EHMT1 on histone 3 | [26] |
MT1G | Modulation of the PI3K/AKT and Rb/E2F signaling pathways | [89] |
MT1, MT2A | Modulation of the PI3K/AKT signaling pathway | [25] |
MT1H | Suppression of the Wnt/β-catenin signaling pathway | [8] |
MT1G | Allelic loss on chromosome 16q12.1-q23.1 | [155] |
MT1F | Loss of heterozygosity | [52] |
MT2A | SNP (rs28336003) | [14] |