GI-Malignancy Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
FEBS J. 2018 Feb;285(4):752-762. doi: 10.1111/febs.14209. Epub 2017 Sep 15.
Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. Nonalcoholic fatty liver disease (NAFLD), a common disorder in obese people, has been identified as an important risk factor for HCC. Following the increasing prevalence of obesity, it is expected that the contribution of NAFLD to HCC's incidence worldwide will grow. Recently, a number of studies have been published, which help us better understand cellular and molecular mechanisms of how NAFLD promotes hepatocarcinogensis. Inflammatory cytokines, ER stress and circadian dysregulation, which mediate hepatocyte injury and NAFLD progression, have been identified to promote malignant transformation of hepatocytes. Besides these 'intrinsic' effects, lipid dysregulation dramatically affects the liver local microenvironment. The reshaped immune environment has also been found to contribute to the NAFLD-mediated hepatocarcinogenesis. This review explores recent findings of both 'intrinsic' effects on hepatocytes and the role of the local environment in NAFLD-promoted HCC development.
肝细胞癌（HCC）是第六种最常见的肿瘤，也是全球癌症相关死亡的第二大主要原因。非酒精性脂肪性肝病（NAFLD）是肥胖人群中的一种常见疾病，已被确定为 HCC 的重要危险因素。随着肥胖症的患病率不断增加，预计 NAFLD 在全球范围内导致 HCC 发病率的贡献将会增加。最近，发表了许多研究，这些研究帮助我们更好地了解 NAFLD 促进肝癌发生的细胞和分子机制。已确定介导肝细胞损伤和 NAFLD 进展的炎症细胞因子、内质网应激和昼夜节律失调会促进肝细胞的恶性转化。除了这些“内在”作用外，脂质失调还会显著影响肝脏局部微环境。重塑的免疫环境也被发现有助于 NAFLD 介导的肝癌发生。本文综述了最近关于 NAFLD 促进 HCC 发展过程中“内在”作用对肝细胞的影响以及局部环境作用的研究进展。
