Malignant transformation of cells drives the development of tumors. Cancer cells can be routinely genotyped today revealing a large number of somatic mutations. However, it remains unclear which mutations contribute to malignant transformation and provide a survival advantage to cancer cells and which are simply passenger mutations. Rather than dissecting each mutation individually by biochemical techniques such as cloning and overexpression, we propose to systematically profile the proteome of cancer cells for altered protein surface accessibility, which can help to better understand the impact of somatic mutations on proteome function and activity. Neomorphic perturbations in protein surface accessibility is revealed with a new, quantitative, in vivo chemical labeling approach coupled to shot gun proteomics. The novel approach can be used as a platform technology to screen patient-derived cancer cells and holds promise to pinpoint critical, cancer cell specific perturbations in the proteome.
We propose a novel technology to rapidly identify and quantify neomorphic, structural changes in the architecture of cancer cell proteomes using in vivo chemical labeling with stable isotopes. The method holds promise to systematically screen cancer cells for perturbed protein surface accessibilities, which helps to understand the impact of somatic mutations on the structure, function and activity of the proteome and to develop targeted cancer therapies.
| Yates 3rd, John R (2018) Content Is King: Databases Preserve the Collective Information of Science. J Biomol Tech 29:1-3 |
