Loss of correlated proteasomal subunit expression selectively promotes the 20S state which underlies luminal breast tumorigenicity.

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.

The interaction network of the proteasome assembly chaperone PSMD9 regulates proteostasis.

Functional networks in cells are created by physical, genetic, and regulatory interactions. Mapping them and annotating their functions by available methods remains a challenge. We use affinity purification mass spectrometry (AP-MS) coupled with SLiMFinder to discern such a network involving 26S proteasome non-ATPase regulatory subunit 9 (PSMD9), a chaperone of proteasome assembly.

PSMD9 ribosomal protein network maintains nucleolar architecture and WT p53 levels.

Capitalizing on an unexpected observation that multiple free ribosomal proteins co-purify/pull-down with PSMD9, we report here for the first time that PSMD9 is necessary to maintain the morphology and integrity of the nucleolus. As seen by NPM1 immunofluorescence and electron microscopy, the nucleolar structure is clearly disrupted in PSMD9 null MCF7 breast cancer cells. The resultant stress is pronounced leading to the accumulation of WT p53 and slow growth.

Metabolomic alterations in invasive ductal carcinoma of breast: A comprehensive metabolomic study using tissue and serum samples.

Invasive ductal carcinoma (IDC) is the most common type of breast cancer and the leading cause of breast cancer related mortality. In the present study, metabolomic profiles of 72 tissue samples and 146 serum samples were analysed using targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM/MS) and untargeted gas chromatography mass spectrometry (GC-MS) approaches. Combination of univariate and multivariate statistical treatment identified significant alterations of 42 and 32 metabolites in tissue and serum samples of IDC, respectively when compared to control.