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Table 1: Metastasis promoters interacting with MDM2
Gene Roles in liver cancer Binding to MDM2 Functional association with References
metastasis MDM2
HIF-1α Overexpression of HIF-1α is Endogenous binding MDM2 positively regulates [32-39]
correlated with vascular invasion HIF-1α expression in MEFs,
and poor survival in human HCC. colon cancer, and osteosarcoma
cell lines independent of p53.
Conversely, MDM2 is reported to
destabilize HIF-1α by promoting
its ubiquitination.
Slug Overexpression of Slug is Endogenous binding MDM2 stabilizes Slug mRNA [41-44]
associated with invasion and in human non-small cell lung
metastasis of HCC by repressing carcinoma and colon cancer cell
E-cadherin. lines.
MMP-9 Overexpression of MMP-9 is Unknown MDM2 increases the MMP-9 [46-49,51,52]
well correlated with invasion, promoter activity in breast cancer
metastasis, and poor prognosis in cell lines.
liver cancer.
HuR/ELAV1 HuR expression is positively Endogenous binding MDM2 neddylates HuR, protects [58,60]
correlated with advanced stages it from degradation, and induces
in HCC and poor outcomes in its nuclear localization in MEFs,
HCC patients. mouse liver progenitor MLP29,
colon cancer RKO, and HCC
HepG2 cell lines.
HCC: hepatocellular carcinoma; MDM2: murine double minute 2; MEFs: mouse embryonic fibroblasts; HuR: Hu antigen R; HIF-1α: hypoxia-inducible factor-1-alpha;
MMP-9: matrix metalloproteinase 9

Table 2: Metastasis suppressors interacting with MDM2
Gene Roles in liver cancer Binding to MDM2 Functional association with MDM2 References
metastasis
E-cadherin Reduced E-cadherin Endogenous binding MDM2 promotes E-cadherin degradation in breast [68-72]
expression is associated cancer cell lines.
with high tumor grade,
vascular invasion,
intrahepatic metastasis,
disease progression, and
poor outcomes.
NME2 NME2 expression is Endogenous binding MDM2 suppresses the ability of NME2 to negatively [77-79]
increased in HCC. regulate cell motility in renal cell carcinoma and lung
cancer cell lines.
TAp63 Role of TAp63 in HCC Endogenous binding MDM2 suppresses TAp63 activity by inhibiting its [91,92,94]
metastasis is not explored. nuclear localization in MEFs and osteosarcoma cell
lines. Conversely, MDM2 increases TAp63 levels
and its transcriptional activity in osteosarcoma and
monkey kidney fibroblast-like cell lines.
FOXO Direct association of Endogenous binding MDM2 degrades FOXO1, 3, and 4 in MEFs, breast [110-112]
family FOXO proteins with HCC cancer, and lung cancer cell lines.
metastasis remains
unknown.
MTBP MTBP inhibits HCC Exogenous The roles of MTBP in cancer metastasis, the [114-117,122]
migration and metastasis underlying mechanisms, and functional association
in ACTN4-dependent and between MDM2 and MTBP remain to be further
-independent manners. investigated.
Controversially, MTBP may
increase HCC metastasis
by stabilizing MDM2.
MDM2: murine double minute 2; FOXO: forkhead box O; NME2: non-metastatic cells 2; MTBP: MDM2 binding protein; HCC: hepatocellular carcinoma

115 Hepatoma Research | Volume 2 | May 6, 2016