Autophagy is an intracellular catabolic process that is increasingly being recognized as a crucial factor in several human diseases including cancers. Mounting evidence suggests that autophagy allows tumor cells to overcome otherwise fatal stresses and to increase dissemination. Nevertheless, how autophagy controls these processes and in particular how it impinges on cell-cell adhesion is still poorly understood. Here, we investigate the role of autophagy in the turnover of the epithelial adhesion molecule E-cadherin in the context of breast cancer. We demonstrated in breast cancer cell lines that autophagy impinges on E-cadherin expression and in the configuration of adherens junctions. Besides, we showed that E-cadherin colocalizes with LC3B and SQSTM1/p62, two components of the autophagosome machinery. Pull down and immunoprecipitation analyses provided evidence that E-cadherin and SQSTM1/p62 physically interact. Moreover, the physical closeness of E-cadherin and SQSTM1/p62 was demonstrated by proximity ligation assays in breast cancer cell lines and primary tumors. Finally, we proved that the silencing of SQSTM1/p62 diminished the E-cadherin/LC3B colocalization, further supporting the role of SQSTM1/p62 in E-cadherin delivery to autophagosomes. These findings suggest that the activation of autophagy, reported in breast cancers with poor prognosis and in dormant breast cancer cells, may contribute to the control of tumor progression via downmodulation of E-cadherin protein levels.

自噬是一种细胞内分解代谢过程，越来越多地被认为是包括癌症在内的几种人类疾病的关键因素。越来越多的证据表明自噬使肿瘤细胞克服了致命的压力并增加了扩散。然而，自噬如何控制这些过程，特别是如何影响细胞与细胞的粘附仍然知之甚少。在这里，我们调查自噬在乳腺癌中上皮粘附分子E-钙粘着蛋白的更新中的作用。我们在乳腺癌细胞系中证明了自噬会影响E-钙黏着蛋白的表达和粘附连接的构型。此外，我们表明E-钙粘着蛋白与自噬体机制的两个组成部分LC3B和SQSTM1 / p62共定位。下拉和免疫沉淀分析提供了E-钙粘蛋白和SQSTM1 / p62物理相互作用的证据。此外，在乳腺癌细胞系和原发性肿瘤中通过邻近结扎法证明了E-钙粘着蛋白和SQSTM1 / p62的物理紧密性。最后，我们证明了SQSTM1 / p62的沉默减少了E-cadherin / LC3B的共定位，进一步支持了SQSTM1 / p62在E-cadherin递送至自噬体中的作用。这些发现表明，在预后较差的乳腺癌和休眠的乳腺癌细胞中报道的自噬激活可能通过下调E-钙粘蛋白水平而有助于控制肿瘤的进展。E-钙粘着蛋白和SQSTM1 / p62的物理亲密性通过在乳腺癌细胞系和原发性肿瘤中的邻近结扎法得到证实。最后，我们证明了SQSTM1 / p62的沉默减少了E-cadherin / LC3B的共定位，进一步支持了SQSTM1 / p62在E-cadherin递送至自噬体中的作用。这些发现表明，在预后较差的乳腺癌和休眠的乳腺癌细胞中报道的自噬激活可能通过下调E-钙粘蛋白水平而有助于控制肿瘤的进展。E-钙粘着蛋白和SQSTM1 / p62的物理亲密性通过在乳腺癌细胞系和原发性肿瘤中的邻近结扎法得到证实。最后，我们证明了SQSTM1 / p62的沉默减少了E-cadherin / LC3B的共定位，进一步支持了SQSTM1 / p62在E-cadherin递送至自噬体中的作用。这些发现表明，在预后较差的乳腺癌和休眠的乳腺癌细胞中报道的自噬激活可能通过下调E-钙粘蛋白水平而有助于控制肿瘤的进展。