Proteomics

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Targeting the Scaffold Protein Plectin by an Organometallic as a Strategy to Inhibit Tumour Invasiveness - cytoplasmic proteins of untreated HCT 116 epithelial cells, 24h

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. 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hct-116 Cell, Colon

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD005373 | Pride | 2022-03-01

REPOSITORIES: Pride

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HCT116_profiling_cyt_control_24h_1_1.mgf Mgf
HCT116_profiling_cyt_control_24h_1_1.mzid.gz Mzid
HCT116_profiling_cyt_control_24h_1_1.pride.mgf.gz Mgf
HCT116_profiling_cyt_control_24h_1_1.pride.mztab.gz Mztab
HCT116_profiling_cyt_control_24h_1_1.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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