Proteomics

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Targeting the Scaffold Protein Plectin by an Organometallic as a Strategy to Inhibit Tumour Invasiveness- whole cell lysate of HCT 116 epithelial cells, Ru-OH-2 competitive pull down 4h

ABSTRACT: 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. Plecstatins possess anti-invasive properties in tumour spheroids and also display tumour-inhibiting effects in vivo after oral administration. The ability of plecstatins to alter the MT network via plectin represents a unique mechanism to target MTs and shows promise as an anticancer strategy. Ru-OH-2 is an analogue of plecstatin-3 displaying an ancillary hydrogen bond donor instead of a hydrogen bond acceptor.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hct-116 Cell, Colon

DISEASE(S): Colon Cancer

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD010319 | Pride | 2022-03-01

REPOSITORIES: Pride

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Action DRS
HCT116_Pulldown_RuOH_competitive_1a.mgf Mgf
HCT116_Pulldown_RuOH_competitive_1a.mzML Mzml
HCT116_Pulldown_RuOH_competitive_1a.mzid.gz Mzid
HCT116_Pulldown_RuOH_competitive_1a.pride.mgf.gz Mgf
HCT116_Pulldown_RuOH_competitive_1a.raw Raw
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Publications

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knoc  ...[more]

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