ABSTRACT
Correction for 'Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy' by Chenxing Fu et al., Nanoscale, 2020, 12, 12126-12132, DOI: .
ABSTRACT
Protein quality control and proteostasis are essential to maintain cell survival as once disordered, they will trigger endoplasmic reticulum (ER) stress and even initiate apoptosis. Severe ER stress-mediated apoptosis is the cause of neurodegenerative diseases and expected to be a new target for cancer therapy. In this study, we designed a small molecule of 1-Nap to execute furin-instructed molecular self-assembly for selectively inhibiting the growth of MDA-MB-468 cells in vitro and in vivo. According to the results of transmission electron microscopy (TEM) and HPLC tracing analysis, 1-Nap is capable of self-assembling upon furin-instructed cleavage that transforms 1-Nap nanoparticles to 1-Nap nanofibers. Fluorescence imaging and Western-blot analysis results indicate that the furin-instructed self-assembly of 1-Nap rather than its ER-targeting interaction is indispensable for the ER stress and activation of apoptosis. The furin-instructed self-assembly of 1-Nap is associated with both the ER (1-Nap's targeting location) and the trans-Golgi network (furin's location); this inspired us to reasonably believe that the blocking of ER-to-Golgi traffic in the secretory pathway by molecular self-assembly may be the intrinsic motivation for controlling cell fate. This work provides a new way for the targeted disturbance of the proteostasis of cells through molecular self-assembly for developing cancer therapeutics.
