Trends in confinement-induced cell migration and multi-omics analysis.

Cell migration is an essential manner of different cell lines that are involved in embryological development, immune responses, tumorigenesis, and metastasis in vivo. Physical confinement derived from crowded tissue microenvironments has pivotal effects on migratory behaviors. Distinct migration modes under a heterogeneous extracellular matrix (ECM) have been extensively studied, uncovering potential molecular mechanisms involving a series of biological processes. Significantly, multi-omics strategies have been launched to provide multi-angle views of complex biological phenomena, facilitating comprehensive insights into molecular regulatory networks during cell migration. In this review, we describe biomimetic devices developed to explore the migratory behaviors of cells induced by different types of confined microenvironments in vitro. We also discuss the results of multi-omics analysis of intrinsic molecular alterations and critical pathway dysregulations of cell migration under heterogeneous microenvironments, highlighting the significance of physical confinement-triggered intracellular signal transduction in order to regulate cellular behaviors. Finally, we discuss both the challenges and promise of mechanistic analysis in confinement-induced cell migration, promoting the development of early diagnosis and precision therapeutics.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial-mesenchymal transition-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading-edge protrusion formation, and the rear-edge recontraction, which coordinates VACV-induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.