The Piezo channel is used by migrating cells to sense compressive load

Migrating cells face varied mechanical and physical barriers in physiological environments, but how they sense and respond to them remains to be fully understood. We used a custom-built ‘cell squasher’ to apply uniaxial pressure to Dictyostelium cells migrating under soft agarose. Within 10 seconds of application, loads of as little as 100 Pa cause cells to move using blebs instead of pseudopods. Cells lose volume and surface area under pressure and their actin dynamics are perturbed. Myosin-II is recruited to the cortex, potentially increasing contractility and so driving blebbing. The blebbing response depends on extra-cellular calcium, is accompanied by increased cytosolic calcium and largely abrogated in null mutants of the Piezo stretch-operated channel. We propose that migrating cells sense mechanical force through mechano-sensitive channels, leading to an influx of calcium and cortical recruitment of myosin, thus re-directing the motile apparatus to produce blebs rather than pseudopods.

Role of bcl-2 in Epstein-Barr Virus-Induced Malignant Conversion of Burkitt's Lymphoma Cell Line Akata

ABSTRACT We have demonstrated that Epstein-Barr virus (EBV) confers enhanced growth capability in soft agarose, tumorigenesis in the SCID mouse, and resistance to apoptosis in the Burkitt's lymphoma cell line Akata. Subsequently, we have shown that EBV-encoded small RNAs (EBERs) are responsible for these phenotypes. We constantly observed the upregulation of bcl-2 oncoprotein expression upon EBV infection and expression of EBERs. To test whether these phenotypes were due to the upregulation of bcl-2 expression, we introduced bcl-2 into EBV-negative Akata cells at various levels encompassing the range at which EBV-positive cells expressed it. As cells expressed bcl-2 at higher levels, they became more capable of growing in soft agarose and became resistant to apoptosis. However, clones expressing bcl-2 at a higher level than EBV-positive Akata cells were negative in the tumorigenesis assay in the SCID mouse. On the other hand, introduction of bax into EBV-positive Akata cells reduced the resistance to apoptosis; however, it failed to reduce the growth capability in soft agarose. These data indicate that EBV targets not only bcl-2, but also an unknown pathway(s) to enhance the oncogenic potential of Akata cells.