Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 Ca²⁺ signals that are inhibited by oncogenic KRas.

ABSTRACT: Changes in the mechanical microenvironment and mechanical signals are observed during tumor progression, malignant transformation, and metastasis. In this context, understanding the molecular details of mechanotransduction signaling may provide unique therapeutic targets. Here, we report that normal breast epithelial cells are mechanically sensitive, responding to transient mechanical stimuli through a two-part calcium signaling mechanism. We observed an immediate, robust rise in intracellular calcium (within seconds) followed by a persistent extracellular calcium influx (up to 30 min). This persistent calcium was sustained via microtubule-dependent mechanoactivation of NADPH oxidase 2 (NOX2)-generated reactive oxygen species (ROS), which acted on transient receptor potential cation channe

SUBMITTER: Pratt SJP 

PROVIDER: S-EPMC7584994 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature