Meléndez-Rodríguez Florinda, Roche Olga, Sanchez-Prieto Ricardo, Aragones Julian
Research Unit, Hospital of Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid, Madrid, Spain.
CIBER de Enfermedades Cardiovasculares, Carlos III Health Institute, Madrid, Spain.
Front Oncol. 2018 Jun 8;8:214. doi: 10.3389/fonc.2018.00214. eCollection 2018.
The most common type of the renal cancers detected in humans is clear cell renal cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene inactivation of the Von Hippel-Lindau (VHL) factor in the renal epithelium, which deregulates the hypoxia-inducible factors (HIFs) HIF1α and HIF2α, and provokes their constitutive activation irrespective of the cellular oxygen availability. While HIF1α can act as a ccRCC tumor suppressor, HIF2α has emerged as the key HIF isoform that is essential for ccRCC tumor progression. Indeed, preclinical and clinical data have shown that pharmacological inhibitors of HIF2α can efficiently combat ccRCC growth. In this review, we discuss the molecular basis underlying the oncogenic potential of HIF2α in ccRCC by focusing on those pathways primarily controlled by HIF2α that are thought to influence the progression of these tumors.
在人类中检测到的最常见的肾癌类型是透明细胞肾细胞癌（ccRCC）。这些肿瘤通常由肾上皮细胞中双等位基因失活的冯·希佩尔-林道（VHL）因子引发，这会使缺氧诱导因子（HIFs）HIF1α和HIF2α失调，并引发它们的组成性激活，而与细胞氧可用性无关。虽然HIF1α可以作为ccRCC肿瘤抑制因子，但HIF2α已成为ccRCC肿瘤进展所必需的关键HIF亚型。事实上，临床前和临床数据表明，HIF2α的药理抑制剂可以有效地对抗ccRCC的生长。在这篇综述中，我们通过关注那些主要由HIF2α控制的、被认为会影响这些肿瘤进展的途径，来讨论HIF2α在ccRCC中致癌潜力的分子基础。
