Molecular mechanisms of liver injury and hepatocarcinogenesis: focusing on the role of stress-activated MAPK.
Molecular mechanisms of liver injury and hepatocarcinogenesis: focusing on the role of stress-activated MAPK.
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DOI：
10.1155/2012/172894
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Maeda S
中科院分区：
文献类型：
--
作者：
Nakagawa H;Maeda S
肝细胞癌（HCC）是癌症死亡的第三大常见原因。近年来，由于早期诊断和治疗的进步，肝癌患者的短期预后有所改善，但长期预后仍不令人满意。因此，进一步了解肝癌的分子致癌机制和独特的致病生物学是非常重要的。肝癌发生中最典型的过程是潜在的慢性肝损伤，其导致肝细胞死亡、炎症和代偿性增殖的重复循环，随后提供导致HCC发展的促有丝分裂和致突变环境。最近的体内研究表明，应激激活的丝裂原活化蛋白激酶（MAPK）级联收敛于c-Jun氨基末端激酶（JNK）和p38在这些过程中起着核心作用，它作为一个治疗靶点引起了相当大的关注。然而，JNK和p38具有复杂的功能和广泛的细胞效应。此外，相互串扰和核因子-κ B通路进一步使这些功能复杂化。充分理解这些观察结果对于将其应用于临床至关重要。本文就应激激活的MAPK通路在肝损伤和肝癌发生中的作用进行综述。
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Short-term prognosis of patients with HCC has improved recently due to advances in early diagnosis and treatment, but long-term prognosis is still unsatisfactory. Therefore, obtaining a further understanding of the molecular carcinogenic mechanisms and the unique pathogenic biology of HCC is important. The most characteristic process in hepatocarcinogenesis is underlying chronic liver injury, which leads to repeated cycles of hepatocyte death, inflammation, and compensatory proliferation and subsequently provides a mitogenic and mutagenic environment leading to the development of HCC. Recent in vivo studies have shown that the stress-activated mitogen-activated protein kinase (MAPK) cascade converging on c-Jun NH2-terminal kinase (JNK) and p38 plays a central role in these processes, and it has attracted considerable attention as a therapeutic target. However, JNK and p38 have complex functions and a wide range of cellular effects. In addition, crosstalk with each other and the nuclear factor-kappaB pathway further complicate these functions. A full understanding is essential to bring these observations into clinical settings. In this paper, we discuss the latest findings regarding the mechanisms of liver injury and hepatocarcinogenesis focusing on the role of the stress-activated MAPK pathway.