Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth.

Breast cancer brain metastases (BCBM) have a 5-20 year latency and account for 30% of mortality; however, mechanisms governing adaptation to the brain microenvironment remain poorly defined. We combine time-course RNA-sequencing of BCBM development with a Drosophila melanogaster genetic screen, and identify Rab11b as a functional mediator of metastatic adaptation. Proteomic analysis reveals that Rab11b controls the cell surface proteome, recycling proteins required for successful interaction with the microenvironment, including integrin β1.

A mechanistic evaluation of the angiogenic properties of a dehydrated amnion chorion membrane in vitro and in vivo.

Angiogenesis is essential for the successful repair of tissues; however, in many chronic conditions, angiogenesis is inhibited. Placental tissues have been shown to illicit an angiogenic response both in vitro and in vivo, and the angiogenic properties of these tissues likely contribute to observed clinical outcomes. Although there is some work describing the angiogenic effects of these tissues, comparatively little has been done to determine the possible mechanisms responsible for this effect.

Combined Scaffold Evaluation and Systems-Level Transcriptome-Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes.

With evolutionary drug resistance impacting efforts to treat disease, the need for small molecules that exhibit novel molecular mechanisms of action is paramount. In this study, we combined scaffold-directed synthesis with a hybrid experimental and transcriptome analysis to identify bis-spirooxindole cyclopropanes that inhibit cancer cell proliferation through disruption of ribosomal function. These findings demonstrate the value of an integrated, biologically inspired synthesis and assay strategy for the accelerated identification of first-in-class cancer therapeutic candidates.

Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling.

Potassium ion channels are critical in the regulation of cell motility. The acquisition of cell motility is an essential parameter of cancer metastasis. However, the role of K channels in cancer metastasis has been poorly studied.

Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer.

Potassium ion (K) channels have been recently found to play a critical role in cancer biology. Despite that pharmacologic manipulation of ion channels is recognized as an important therapeutic approach, very little is known about the effects of targeting of K channels in cancer. In this study, we demonstrate that use of the Kv11.

Spatiotemporal patterning of polyamines in Drosophila development.

While several studies have implicated polyamines (PAs) in development, little research has been done in genetically tractable model systems like Drosophila. Here, we integrate transcriptional and metabolic data across Drosophila development, and are the first to show temporal, stage-specific regulation of PA accumulation in embryonic trachea and eye discs using immunohistochemistry. Understanding the regulation driving this accumulation can provide insight into PA metabolism and transport.