Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics

作者：Wang, J.; Cai, J.; Huang, Y.; Ke, Q.; Wu, B.; Wang, S.; Han, X.; Wang, T.; Wang, Y.; Li, W.; Lao, C.; Song, W.; Xiang, A. P.^*

来源：Oncogene, 2016, 35(24): 3139-3150.

DOI：10.1038/onc.2015.370

• INTERMEDIATE-FILAMENT NESTIN
• PLURIPOTENT STEM-CELLS
• OXIDATIVE STRESS
• TARGETING MITOCHONDRIA
• CANCER-THERAPY
• MORPHOLOGY
• EXPRESSION
• ROS
• PHOSPHORYLATION
• VIMENTIN

Nestin is widely expressed in numerous tumors and has become a diagnostic and prognostic indicator. However, the exact mechanism by which nestin contributes to tumor malignancy remains poorly understood. Here, we found marked upregulation of nestin expression in highly proliferative and invasive gastrointestinal stromal tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative and invasive activity owing to a decrease of mitochondrial intracellular reactive oxygen species (ROS) generation. Furthermore, nestin was co-localized with mitochondria, and knockdown of nestin increased mitochondrial elongation and influenced the mitochondrial function, including oxygen consumption rates, ATP generation and mitochondrial membrane potential and so on. In exploring the underlying mechanism, we demonstrated nestin knockdown inhibited the mitochondrial recruitment of Dynamin-related protein1 and induced the change of mitochondrial dynamics. Thus, nestin may have an important role in GIST malignancy by regulating mitochondrial dynamics and altering intracellular ROS levels. The findings provide new clues to reveal mechanisms by which nestin mediates the proliferation and invasion of GISTs.

• 出版日期2016-6-16
• 单位北京协和医学院; 中山大学; 广州市妇女儿童医疗中心; 中国医学科学院阜外医院