Mouse ERα(Estrogen Receptor Alpha) ELISA Kit

While knowledge of protein-protein interactions (PPIs) is critical for understanding virus-host relationships, limitations on the scalability of high-throughput methods have hampered their identification beyond a number of well-studied viruses. Here, we implement an in silico computational framework (pathogen host interactome prediction using structure similarity [P-HIPSTer]) that employs structural information to predict similar to 282,000 pan viral-human PPIs with an experimental validation rate of similar to 76%. In addition to rediscovering known biology, P-HIPSTer has yielded a series of new findings: the discovery of shared and unique machinery employed across human-infecting viruses, a likely role for ZIKV-ESR1 interactions in modulating viral replication, the identification of PPIs that discriminate between human papilloma viruses (HPVs) with high and low oncogenic potential, and a structure-enabled history of evolutionary selective pressure imposed on the human proteome. Further, P-HIPSTer enables discovery of previously unappreciated cellular circuits that act on human-infecting viruses and provides insight into experimentally intractable viruses.

Triple-negative breast cancer (TNBC) accounts for 10 to 20% of breast cancer, with chemotherapy as its mainstay of treatment due to lack of well-defined targets, and recent genomic sequencing studies have revealed a paucity of TNBC-specific mutations. Recurrent gene fusions comprise a class of viable genetic targets in solid tumors; however, their role in breast cancer remains underappreciated due to the complexity of genomic rearrangements in this cancer. Our interrogation of the whole-genome sequencing data for 215 breast tumors catalogued 99 recurrent gene fusions, 57% of which are cryptic adjacent gene rearrangements (AGRs). The most frequent AGRs, BCL2L14-ETV6, TTC6-MIPOL1, ESR1-CCDC170, and AKAP8-BRD4, were preferentially found in the more aggressive forms of breast cancers that lack well-defined genetic targets. Among these, BCL2L14-ETV6 was exclusively detected in TNBC, and interrogation of four independent patient cohorts detected BCL2L14-ETV6 in 4.4 to 12.2% of TNBC tumors. Interestingly, these fusion-positive tumors exhibit more aggressive histopathological features, such as gross necrosis and high tumor grade. Amid TNBC subtypes, BCL2L14-ETV6 is most frequently detected in the mesenchymal entity, accounting for similar to 19% of these tumors. Ectopic expression of BCL2L14-ETV6 fusions induce distinct expression changes from wild-type ETV6 and enhance cell motility and invasiveness of TNBC and benign breast epithelial cells. Furthermore, BCL2L14-ETV6 fusions prime partial epithelial-mesenchymal transition and endow resistance to paclitaxel treatment. Together, these data reveal AGRs as a class of underexplored genetic aberrations that could be pathological in breast cancer, and identify BCL2L14-ETV6 as a recurrent gene fusion in more aggressive form of TNBC tumors.