Vess, A. | Search bioRxiv

bioRxiv2020

Methylglyoxal induces nuclear accumulation of p53 and γH2AX in normal and cancer cells

The formation and accumulation of methylglyoxal (MGO) is associated with age-related diseases such as diabetes, cancer and neurodegenerative disorders. MGO is the major precursor of non-enzymatic glycation of macromolecules affecting their function and structure. We now show for the first time that MGO stress not only led to cellular aging responses like DNA double-strand breaks indicated by an accumulation of {gamma}H2AX in the nucleus. We also observed an immediate increase of Ser15 phosphorylated p53 in the nucleus of MGO treated cell lines which will change the cellular expression pattern with adverse effects on the cell cycle and other cellular functions not necessarily related to aging.

cell biology↗

bioRxiv2017

Dual Phenotype Of MDA-MB-468 Cancer Cells Reveals Mutual Regulation Of Tensin3 And Adhesion Plasticity

Plasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced on mRNA and protein level in suspension cells. Furthermore, challenging breast cancer cells transiently with non-adherent conditions markedly reduces Tns3 expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental cells results in defective adhesion, spreading and migration. Tns3 knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a critical focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.\n\nSummary statementWe identify the cell-matrix adapter protein tensin3 as a determinant of adhesion plasticity, using cancer cells selected for non-adherent growth. Tensin3 expression constitutes a feedback loop controlling adhesion and motility.

cell biology↗