Hedgehog signaling enables repair of ribosomal DNA double-strand breaks.

Ribosomal DNA (rDNA) consists of highly repeated sequences that are prone to incurring damage. Delays or failure of rDNA double-strand break (DSB) repair are deleterious, and can lead to rDNA transcriptional arrest, chromosomal translocations, genomic losses, and cell death. Here, we show that the zinc-finger transcription factor GLI1, a terminal effector of the Hedgehog (Hh) pathway, is required for the repair of rDNA DSBs.

The Pros and Cons of Incorporating Transcriptomics in the Age of Precision Oncology.

The treatment of cancer continues to evolve toward personalized therapies based on individual patient and tumor characteristics. Our successes and failures in adopting a precision-oncology approach have demonstrated the utmost importance in identifying the proper predictive biomarkers of response. Until recently, most biomarkers were identified using immunohistochemistry for protein expression or single-gene analysis to identify targetable alterations.

First-Line Treatment of Widely Metastatic -Mutated Salivary Duct Carcinoma With Combined BRAF and MEK Inhibition.

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy for which limited data exist to guide treatment decisions. With the advent of advanced molecular testing and tumor genomic profiling, clinicians now have the ability to identify potential therapeutic targets in difficult-to-treat cancers such as SDC. This report presents a male patient with widely metastatic SDC found on targeted next-generation sequencing to have a p.

Developing Cures: Targeting Ontogenesis in Cancer.

Cancer has long been known to histologically resemble developing embryonic tissue. Since this early observation, a mounting body of evidence suggests that cancer mimics or co-opts developmental processes to facilitate tumor initiation and progression. Programs important in both normal ontogenesis and cancer progression broadly fall into three domains: the lineage commitment of pluripotent stem cells, the appropriation of primordial mechanisms of cell motility and invasion, and the influence of multiple aspects of the microenvironment on the parenchyma.

TRIP6 regulates p27 KIP1 to promote tumorigenesis.

TRIP6 is an adaptor protein that regulates cell motility and antiapoptotic signaling. Although it has been implicated in tumorigenesis, the underlying mechanism remains largely unknown. Here we provide evidence that TRIP6 promotes tumorigenesis by serving as a bridge to promote the recruitment of p27(KIP1) to AKT in the cytosol.

TRIP6: an adaptor protein that regulates cell motility, antiapoptotic signaling and transcriptional activity.

Thyroid hormone receptor interacting protein 6 (TRIP6), also known as zyxin-related protein-1 (ZRP-1), is an adaptor protein that belongs to the zyxin family of LIM proteins. TRIP6 is primarily localized in the cytosol or focal adhesion plaques, and may associate with the actin cytoskeleton. Additionally, it is capable of shuttling to the nucleus to serve as a transcriptional coregulator.

The adaptor protein TRIP6 antagonizes Fas-induced apoptosis but promotes its effect on cell migration.

The Fas/CD95 receptor mediates apoptosis but is also capable of triggering nonapoptotic signals. However, the mechanisms that selectively regulate these opposing effects are not yet fully understood. Here we demonstrate that the activation of Fas or stimulation with lysophosphatidic acid (LPA) induces cytoskeletal reorganization, leading to the association of Fas with actin stress fibers and the adaptor protein TRIP6.