Lafont Elodie
Inserm U1242, Université de Rennes, 35042 Rennes, France.
Centre de Lutte Contre le Cancer Eugène Marquis, 35042 Rennes, France.
Cancers (Basel). 2020 Apr 29;12(5):1113. doi: 10.3390/cancers12051113.
Throughout tumour progression, tumour cells are exposed to various intense cellular stress conditions owing to intrinsic and extrinsic cues, to which some cells are remarkably able to adapt. Death Receptor (DR) signalling and the Unfolded Protein Response (UPR) are two stress responses that both regulate a plethora of outcomes, ranging from proliferation, differentiation, migration, cytokine production to the induction of cell death. Both signallings are major modulators of physiological tissue homeostasis and their dysregulation is involved in tumorigenesis and the metastastic process. The molecular determinants of the control between the different cellular outcomes induced by DR signalling and the UPR in tumour cells and their stroma and their consequences on tumorigenesis are starting to be unravelled. Herein, I summarize the main steps of DR signalling in relation to its cellular and pathophysiological roles in cancer. I then highlight how the UPR and DR signalling control common cellular outcomes and also cross-talk, providing potential opportunities to further understand the development of malignancies.
在肿瘤进展过程中,由于内在和外在信号,肿瘤细胞会暴露于各种强烈的细胞应激条件下,其中一些细胞能够显著地适应这些条件。死亡受体(DR)信号传导和未折叠蛋白反应(UPR)是两种应激反应,它们都调节着大量的结果,从增殖、分化、迁移、细胞因子产生到细胞死亡的诱导。这两种信号传导都是生理组织稳态的主要调节因子,它们的失调与肿瘤发生和转移过程有关。肿瘤细胞及其基质中由DR信号传导和UPR诱导的不同细胞结果之间控制的分子决定因素及其对肿瘤发生的影响正开始被揭示。在此,我总结了DR信号传导与其在癌症中的细胞和病理生理作用相关的主要步骤。然后,我强调了UPR和DR信号传导如何控制共同的细胞结果以及相互作用,为进一步理解恶性肿瘤的发展提供了潜在机会。