Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells.,Cellular Signalling

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Autophagy induction impairs Wnt/β-catenin signalling through β-catenin relocalisation in glioblastoma cells.
Cellular Signalling ( IF 4.4 ) Pub Date : 2018-10-26 , DOI: 10.1016/j.cellsig.2018.10.017
Barbara Colella ₁ , Fiorella Faienza ₂ , Marianna Carinci ₃ , Giuseppina D'Alessandro ₄ , Myriam Catalano ₅ , Antonio Santoro ₆ , Francesco Cecconi ₇ , Cristina Limatola ₅ , Sabrina Di Bartolomeo ₁

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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/β-catenin signalling is responsible for tumour proliferation, invasion, and stemness maintenance. Here we show that autophagy negatively regulates Wnt/β-catenin signalling in glioblastoma multiforme (GBM) cells, through Dishevelled degradation. We also provide the first evidence that autophagy promotes β-catenin relocalisation within the cell, by inducing a decrease of the nuclear protein fraction. In particular, upon autophagy induction, β-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 β-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.

中文翻译：

自噬诱导通过胶质母细胞瘤细胞中β-catenin的重新定位来削弱Wnt /β-catenin的信号传导。

自噬是一种保守的进化过程，介导溶酶体降解细胞质物质。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的双重作用中，其参与癌症进展是极富争议的。关于自噬和细胞内信号通路之间的相互影响，以及自噬对信号分子更新的影响知之甚少。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，我们显示自噬通过Disheveled降解负调控多形性胶质母细胞瘤（GBM）细胞中的Wnt /β-catenin信号传导。我们还提供了自噬促进细胞内β-catenin重新定位的第一个证据，通过诱导核蛋白部分的减少。特别地，在自噬诱导后，β-连环蛋白主要出现在亚膜区域，与N-钙黏着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，并导致GBM细胞内的β-catenin重新定位。这些发现进一步支持了自噬调节可以代表一种潜在的治疗策略来对比GBM进展的想法。自噬诱导导致Wnt信号减弱，并导致GBM细胞内β-catenin重新定位。这些发现进一步支持了自噬调节可以代表一种潜在的治疗策略来对比GBM进展的想法。自噬诱导导致Wnt信号减弱，并导致GBM细胞内β-catenin重新定位。这些发现进一步支持了自噬调节可以代表一种潜在的治疗策略来对比GBM进展的想法。

更新日期：2018-10-26

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