Targeting the Scaffold Protein Plectin by an Organometallic as a Strategy to Inhibit Tumour Invasiveness- whole cell lysate of HCT 116 epithelial cells, plestatins-3 normal pull down 19h

The inability of determining direct molecular targets of metal-based therapeutic agents beyond the platinum class is one of the major bottlenecks in their development. Here, we employ an integrated chemical proteomics and response profiling approach to identify and validate plestatins, based on an organometallic ruthenium(II) scaffold, as selective plectin-targeting agents. Plectin is a giant scaffold protein involved in controlling cytoarchitecture. Subcytotoxic concentrations of plestatins induce drastic morphological phenotypes on the microtubule (MT) network accompanied by a global down-regulation of translational activity. Plestatins possess anti-invasive properties in tumour spheroids and also display tumour-inhibiting effects in vivo after oral administration. The ability of plestatins to alter the MT network via plectin represents a unique mechanism to target MTs and shows promise as an anticancer strategy.