Nuclear export inhibition jumbles epithelial-mesenchymal states and gives rise to migratory disorder in healthy epithelia.

ABSTRACT: Dynamic nucleocytoplasmic transport of E-M factors regulates cellular E-M states; yet, it remains unknown how simultaneously trapping these factors affects epithelia at the macroscale. To explore this question, we performed nuclear export inhibition (NEI) via leptomycin B and Selinexor treatment, which biases nuclear localization of CRM1-associated E-M factors. We examined changes in collective cellular phenotypes across a range of substrate stiffnesses. Following NEI, soft substrates elevate collective migration of MCF10A cells for up to 24 hr, while stiffer substrates reduce migration at all time points. Our results suggest that NEI disrupts migration through competition between intercellular adhesions and mechanoactivation, generally causing loss of cell-cell coordination. Specifically,

SUBMITTER: Krull CM 

PROVIDER: S-EPMC9943065 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature