Disruption of desmosome function leads to increased centrosome clustering in 14‐3‐3γ‐knockout cells with supernumerary centrosomes

Abstract

14‐3‐3 proteins are conserved, dimeric, acidic proteins that regulate multiple cellular pathways. Loss of either 14‐3‐3ε or 14‐3‐3γ leads to centrosome amplification. However, we find that while the knockout of 14‐3‐3ε leads to multipolar mitoses, the knockout of 14‐3‐3γ results in centrosome clustering and pseudo‐bipolar mitoses. 14‐3‐3γ knockouts demonstrate compromised desmosome function and a decrease in keratin levels, leading to decreased cell stiffness and an increase in centrosome clustering. Restoration of desmosome function increased multipolar mitoses, whereas knockdown of either plakoglobin or keratin 5 led to decreased cell stiffness and increased pseudo‐bipolar mitoses. These results suggest that the ability of the desmosome to anchor keratin filaments maintains cell stiffness, thus inhibiting centrosome clustering, and that phenotypes observed upon 14‐3‐3 loss reflect the dysregulation of multiple pathways.

YWHAG acts as a prognostic marker and is correlated with immune infiltration and cell metastasis in pancreatic cancer

“…In glioblastoma, silencing YWHAG inhibited migration and invasion 38 . The knockdown of YWHAG led to centrosome clustering and further regulated the cell cycle 39 . It has been reported that YWHAG could bind to Rac1, which has been shown to associate with the cytoskeleton and regulate cytoskeleton remodeling and cell migration 40 .…”