Table 2 Overview of the dysregulated expression and functions of MT isoforms in cancer

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

[84, 85]

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

[24, 125]

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]