The role of Atg5 gene in tumorigenesis

• Main Authors: Yin-PingWang, 王尹平
• Other Authors: Hsiao-Sheng Liu
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/zud87u

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 104 === Tumorigenesis is a dynamic and complex process of tumor development, which can be regulated by autophagy. Autophagy is a mechanism by which organelles, proteins and other cytoplasmic components are degraded to maintain cellular homeostasis. Autophagy related 5 (Atg5) is essential for autophagy and plays an important role in autophagosome formation. Increasing evidence suggests that Atg5 also plays autophagy-independent roles in various cellular functions, including apoptosis, immunity and mitosis. We previously demonstrated that activated autophagy suppressed bladder tumor formation accompanied with increased Atg5 protein expression, indicating that autophagy and/or Atg5 plays a suppressive role in tumor formation. The role of Atg5 protein affects tumorigenesis without autophagy is unclear. Therefore, we aim to reveal the autophagy-independent role of Atg5 and its underlying mechanisms in tumorigenesis. An autophagy-deficient Atg7-/- mouse embryonic fibroblast cell line was used to overexpress Atg5 transgene and two stable clones were established to explore the single gene effect of Atg5. We found that Atg5 overexpression increased cell proliferation, colony formation and migration under autophagy deprivation conditions. However, recovery of autophagy by Atg7 transfection reversed the results, implicating that Atg5 might have dual roles in the absence and the presence of autophagy. In vivo animal experiment also showed that Atg5 improved tumor formation in subcutaneous, but the tumor failed to progress and regressed within twelve days. Moreover, we further explored the underlying mechanism and found the increased expression of secreted Wnt5a and p-JNK, but the decreased expression of-catenin. In summary, Atg5 promotes tumorigenesis in vitro and in vivo in an autophagy-independent manner.