Botti Joëlle, Djavaheri-Mergny Mojgan, Pilatte Yannick, Codogno Patrice
INSERM U756, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France.
Autophagy. 2006 Apr-Jun;2(2):67-73. doi: 10.4161/auto.2.2.2458. Epub 2006 Apr 29.
The downregulation of macroautophagy observed in cancer cells is associated with tumor progression. The regulation of macroautophagy by signaling pathways overlaps with the control of cell growth, proliferation, cell survival and death. Several tumor suppressor genes (PTEN, TSC2 and p53) involved in the mTOR signaling network have been shown to stimulate autophagy. In contrast, the oncoproteins involved in this network have the opposite effect. These findings, together with the discovery that haploinsufficiency of the tumor suppressor beclin 1 promotes tumorigenesis in various tissues in transgenic mice, give credibility to the idea that autophagy is a tumor suppressor mechanism. The induction of macroautophagy by cancer treatments may also contribute to cell eradication. However, cancer cells sometimes mobilize autophagic capacities in response to various stimuli without a fatal outcome, suggesting that they can also exploit macroautophagy for their own benefit.
在癌细胞中观察到的巨自噬下调与肿瘤进展相关。信号通路对巨自噬的调控与细胞生长、增殖、细胞存活和死亡的控制相互重叠。参与mTOR信号网络的几个肿瘤抑制基因（PTEN、TSC2和p53）已被证明可刺激自噬。相反，参与该网络的癌蛋白则具有相反的作用。这些发现，连同肿瘤抑制因子Beclin 1的单倍剂量不足会促进转基因小鼠各种组织中的肿瘤发生这一发现，使自噬是一种肿瘤抑制机制这一观点具有可信度。癌症治疗对巨自噬的诱导也可能有助于清除细胞。然而，癌细胞有时会响应各种刺激而调动自噬能力，却没有致命后果，这表明它们也可以利用巨自噬为自身谋利。
