Biology subjects

Plutoni, C.

Publications and source records attributed to Plutoni, C..

3 recordsLinked to original sources

bioRxiv2025

An extended and apical supracellular actin network interconnects squamous carcinoma cells

Epithelial tissues form protective barriers while supporting critical functions such as absorption and secretion. Their structural and functional integrity relies on adherens junctions, which coordinate migration and transmit forces between adjacent cells by connecting their actin cytoskeleton. In this study, we report the presence of an apical supracellular actin network in squamous epithelial cells. Using squamous carcinoma A431 cells as a model, we characterized this network composed of star-shaped actin structures interconnected by linear actin bundles that span multiple cells. We demonstrate that the networks formation and maintenance require actomyosin contractility and intact adherens junctions, while tight junctions seem dispensable. Furthermore, this network dynamically reorganizes as cells migrate and preferentially aligns with the direction of movement. This contractile structure generates mechanical tension that extends across the apical surface of multiple cells. Our findings suggest that this supracellular actin network functions as a long-range force transmission device in squamous cells, advancing our understanding of the biomechanical properties of epithelia.

cell biology↗

bioRxiv2022

MAP4K4 regulates biomechanical forces at adherens junctions and focal adhesions to promote collective cell migration

Collective cell migration is important for normal development and tissue homeostasis, but can also promote cancer metastasis. To migrate collectively, cells need to coordinate their protrusion formation, rear retraction, adhesion sites dynamics, as well as forces generation and transmission. Nevertheless, the regulatory mechanisms coordinating these processes remain elusive. Using the A431 carcinoma cell line, we identify the kinase MAP4K4 as a central regulator of collective migration. We show that MAP4K4 inactivation blocks the migration of clusters while its overexpression decreases cluster cohesion. MAP4K4 regulates protrusion and retraction dynamics, remodels the actomyosin cytoskeleton, and controls the stability of both cell-cell and cell substrate adhesion. MAP4K4 promotes focal adhesion disassembly through the phosphorylation of Moesin, an actin and plasma membrane cross-linker, but disassembles adherens junctions through a Moesin-independent mechanism. By analyzing traction and intercellular forces, we found that the stabilization of adhesion sites in MAP4K4 loss of function leads to a tensional disequilibrium throughout the cell cluster, increasing the traction forces exerted onto the substrate and the tension loading at the cell-cell adhesions. Together, our results indicates that MAP4K4 activity is a key regulator of biomechanical forces at adhesion sites, promoting collective migration.

cell biology↗

bioRxiv2019

Quantitative proteomics identifies novel PIAS1 protein substrates involved in cell migration and motility

The Protein Inhibitor of Activated STAT 1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways, including STAT signaling, p53 pathway, and the steroid hormone signaling pathway. PIAS1 can SUMOylate PML (at Lys-65 and Lys-160) and PML-RAR promoting their ubiquitin-mediated degradation. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. To understand the mechanism of action of PIAS1, we developed a quantitative SUMO proteomic approach to identify potential substrates of PIAS1 in a system-wide manner. Our analyses enabled the profiling of 983 SUMO sites on 544 proteins, of which 204 SUMO sites on 123 proteins were identified as putative PIAS1 substrates. These substrates are involved in different cellular processes, such as transcriptional regulation, DNA binding and cytoskeleton dynamics. Further functional studies on Vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, revealed that PIAS1 exerts its effects on cell migration and cell invasion through the SUMOylation of VIM at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly, and cells expressing a non-SUMOylatable VIM mutant showed reduced levels of proliferation and migration. Our approach not only provides a novel strategy for the identification of E3 SUMO ligase substrates, but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.

cancer biology↗