Ranjan Atul, Bera Kaustav, Iwakuma Tomoo
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Hepatoma Res. 2016;2:114-121. doi: 10.20517/2394-5079.2015.67. Epub 2016 May 6.
Hepatocellular carcinoma (HCC) has emerged as one of the most commonly diagnosed forms of human cancer; yet, the mechanisms underlying HCC progression remain unclear. Unlike other cancers, systematic chemotherapy is not effective for HCC patients, while surgical resection and liver transplantation are the most viable treatment options. Thus, identifying factors or pathways that suppress HCC progression would be crucial for advancing treatment strategies for HCC. The murine double minute 2 (MDM2)-p53 pathway is impaired in most of the cancer types, including HCC, and MDM2 is overexpressed in approximately 30% of HCC. Overexpression of MDM2 is reported to be well correlated with metastasis, drug resistance, and poor prognosis of multiple cancer types, including HCC. Importantly, these correlations are observed even when p53 is mutated. Indeed, p53-independent functions of overexpressed MDM2 in cancer progression have been suitably demonstrated. In this review article, we summarize potential effectors of MDM2 that promote or suppress cancer metastasis and discuss the p53-independent roles of MDM2 in liver cancer metastasis from clinical as well as biological perspectives.
肝细胞癌（HCC）已成为人类癌症中最常见的诊断形式之一；然而，HCC进展的潜在机制仍不清楚。与其他癌症不同，系统化疗对HCC患者无效，而手术切除和肝移植是最可行的治疗选择。因此，识别抑制HCC进展的因素或途径对于推进HCC的治疗策略至关重要。鼠双微体2（MDM2）-p53通路在包括HCC在内的大多数癌症类型中受损，并且MDM2在约30%的HCC中过表达。据报道，MDM2的过表达与包括HCC在内的多种癌症类型的转移、耐药性和不良预后密切相关。重要的是，即使p53发生突变，这些相关性仍然存在。事实上，过表达的MDM2在癌症进展中的p53非依赖性功能已得到充分证实。在这篇综述文章中，我们总结了促进或抑制癌症转移的MDM2潜在效应器，并从临床和生物学角度讨论了MDM2在肝癌转移中的p53非依赖作用。
