Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells
Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells
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DOI：
10.1016/j.cellsig.2018.10.017
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Di Bartolomeo, Sabrina
中科院分区：
文献类型：
--
作者：
Colella, Barbara;Faienza, Fiorella;Di Bartolomeo, Sabrina
Autophagy is an evolutionary conserved process mediating lysosomal degradation of cytoplasmic material.由于其在限制肿瘤转化和保护已建立的肿瘤细胞免受不利条件影响方面的双重作用，它在癌症进展中的参与备受争议。关于自噬和细胞内信号通路之间的交互作用，以及自噬对信号分子周转的影响，人们知之甚少。异常激活的 Wnt/β-catenin 信号传导负责肿瘤的增殖、侵袭和干性维持。在这里，我们发现自噬通过不规则的降解对多形性胶质母细胞瘤 (GBM) 细胞中的 Wnt/β-连环蛋白信号传导产生负调节。我们还提供了第一个证据，证明自噬通过诱导核蛋白部分减少，促进细胞内 β-连环蛋白的重新定位。特别是，在自噬诱导后，D-连环蛋白主要集中在膜下区域，与 N-钙粘蛋白结合形成上皮样细胞-细胞粘附结构。我们的数据首次表明，自噬诱导导致 Wnt 信号减弱和 GBM 细胞内的 β-连环蛋白重新定位。这些发现进一步支持了这样的观点：自噬调节可能代表一种对抗 GBM 进展的潜在治疗策略。
Autophagy is an evolutionary conserved process mediating lysosomal degradation of cytoplasmic material. Its involvement in cancer progression is highly controversial, due to its dual role in both limiting tumoural transformation and in protecting established tumoral cells from unfavorable conditions. Little is known about the cross-talk between autophagy and intracellular signalling pathways, as well as about autophagy impact on signalling molecules turnover.An aberrantly activated Wnt/beta-catenin signalling is responsible for tumour proliferation, invasion, and stemness maintenance. Here we show that autophagy negatively regulates Wnt/beta-catenin signalling in glioblastoma multiforme (GBM) cells, through Dishevelled degradation. We also provide the first evidence that autophagy promotes beta-catenin relocalisation within the cell, by inducing a decrease of the nuclear protein fraction. In particular, upon autophagy induction, D-catenin appears mainly localized in sub-membrane areas where it associates with N-cadherin to form epithelial-like cell-cell adhesion structures.Our data indicate, for the first time, that autophagy induction results in Wnt signalling attenuation and in beta-catenin relocalisation within the GBM cell. These findings further support the idea that autophagy modulation could represent a potential therapeutical strategy to contrast GBM progression.