Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis

Speaker: 賴曉菁                           Date: 15:10~16:00; May 10, 2006

Commentator: 楊倍昌 老師                  Place: Room: 601

Abstract:

    Apoptosis, autophagy, and necrosis are three different types of cell death. Autophagy is a cellular process that cell self-digest intracellular organelles. In human tumor, metabolic stress is a common phenomenon and has the potential to induce apoptotic cell death. But in apoptosis-deficient tumor cell, metabolic stress can induce autophagy instead of apoptosis suggesting that autophagy possibly supports survival under metabolic stress. It has been proved that type I PI3 kinases and their downstream signal transduction component, AKt and TOR, have been implicated in suppressing autophagy. In contrast, type III PI3 kinases and one of their interacting proteins, Beclin1, participates in the induction of autophagy (2). The authors demonstrate that inhibition of autophagy by AKT activation or beclin1 destruction promotes epithelial tumorigenesis in the presence or absence of apoptosis. When apoptosis and autophagy are disabled, tumor cell went through necrosis under metabolic stress and this necrosis is associated with inflammation which has the potential to accelarate tumor growth and associated with poor prognosis (3). Autophagy has been detected in the center of the tumor mass, where is unvascularized and is metabolic stressed. All together autophagy may suppression tumorigenesis by mitigating metaboloic stress and work together with apoptosis, by preventing death by necrosis.

References:

1.      Degenharat K., Mathew R., Beaudoin B., Bray K., Anderson A., Chen G., Mukherjee C., Shi Y., Gelinas C., Fan Y., Nelson DA., Jin S., White E. (2006). Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10, 51-64.

2.      Edinger, AL., and Thompson CB. (2003). Defective autophagy leads to cancer. Cancer cell 4, 422-424.

3.      Vakkia, J., and Lotze MT., (2004). Inflammation and necrosis promote tumor groeth. Nat. Rev. Immunol. 4, 641-648