Miyazaki Toshiaki, Bub Jeffrey D, Uzuki Miwa, Iwamoto Yoshiki
Department of Urology, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, 53226-0509, USA.
Biochem Biophys Res Commun. 2005 Jul 22;333(1):79-87. doi: 10.1016/j.bbrc.2005.05.076.
Adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Adiponectin occurs in non-proteolytic (full-length adiponectin: f-adiponectin) and proteolytic (globular adiponectin: g-adiponectin) forms in various oligomeric states. Different forms of adiponectin show distinct biological effects through differential activation of downstream signaling pathways. Here we identify c-Jun NH(2)-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT3) as common downstream effectors of f- and g-adiponectin. f- and g-adiponectin both stimulate JNK activation in prostate cancer DU145, PC-3, and LNCaP-FGC cells, hepatocellular carcinoma HepG2 cells, and C2C12 myoblasts. Furthermore, both f- and g-adiponectin drastically suppress constitutive STAT3 activation in DU145 and HepG2 cells. These suggest that JNK and STAT3 may constitute a universal signaling pathway to mediate adiponectin's pathophysiological effects on metabolic syndrome and cancer.
脂联素是一种主要的脂肪细胞因子，通过作用于肌肉细胞和肝细胞等细胞类型，在抑制代谢综合征中发挥关键作用。此外，有证据表明脂联素可能影响癌症的发病机制。脂联素以非蛋白水解形式（全长脂联素：f-脂联素）和蛋白水解形式（球状脂联素：g-脂联素）存在于各种寡聚状态中。不同形式的脂联素通过下游信号通路的差异激活表现出不同的生物学效应。在此，我们确定c-Jun氨基末端激酶（JNK）和信号转导及转录激活因子3（STAT3）是f-脂联素和g-脂联素共同的下游效应器。f-脂联素和g-脂联素均能刺激前列腺癌DU145、PC-3和LNCaP-FGC细胞、肝癌HepG2细胞以及C2C12成肌细胞中的JNK激活。此外，f-脂联素和g-脂联素均能显著抑制DU145和HepG2细胞中组成型STAT3的激活。这些表明JNK和STAT3可能构成一条通用的信号通路，以介导脂联素对代谢综合征和癌症的病理生理作用。
