Roseline Godbout

Significance: HER2-enriched breast cancers are aggressive and often develop resistance to the standard drug trastuzumab. Although these cancers frequently possess the genes necessary to respond to Retinoic Acid (RA) therapy, they often remain resistant to it. In this study, we identified the oncoprotein MYC as a key driver of this resistance. We found that high levels of MYC suppress the production of CRABP2, a transport protein required to shuttle RA into the cell nucleus.

Importantly, we demonstrated that depleting MYC restores sensitivity to RA and, when combined with RA treatment, significantly enhances the effectiveness of trastuzumab. This research suggests that screening for MYC levels could help identify patients who would benefit most from combined RA and trastuzumab therapy.

Significance: Glioblastoma Stem-like Cells (GSCs) are often responsible for tumor recurrence and resistance to therapy. This study identifies a specific subpopulation of "migratory" GSCs that drive tumor infiltration. We discovered that the protein FABP7 is key to this process. When activated by polyunsaturated fatty acids (PUFAs), FABP7 triggers a signaling pathway involving the nuclear receptor RXRα. This pathway upregulates stemness (SOX2) and invasion (ZEB1) factors, transforming stationary stem cells into highly migratory ones.

Inhibiting this FABP7-RXRα pathway successfully reduced tumor infiltration in our models, highlighting a promising new therapeutic target.

Significance: This landmark study, published in the prestigious journal Nature Communications, reveals why DDX1 is absolutely essential for life. We discovered that DDX1 knockout embryos fail to develop past the 2-4 cell stage due to catastrophic mitochondrial dysfunction.

Using sophisticated live-cell imaging and molecular analyses, we found that DDX1 forms specialized vesicles that regulate calcium-dependent mitochondrial function during the earliest stages of embryonic development. In the absence of DDX1, mitochondria fragment abnormally, produce excessive reactive oxygen species (ROS), and lose their membrane potential - ultimately leading to developmental arrest. This work establishes DDX1 as a critical regulator of the fundamental cellular processes that enable life and provides insights into potential causes of early embryonic lethality and mitochondrial diseases.

Significance: This groundbreaking study reveals a fundamental cellular survival mechanism. We discovered that DDX1, an RNA helicase, acts as a molecular guardian during cellular stress by forming protective cytoplasmic structures around critical stress response mRNAs.

When cells experience oxidative stress (such as from chemotherapy, radiation, or environmental toxins), DDX1 rapidly relocates from the nucleus to the cytoplasm where it assembles into distinct vesicles containing stress-responsive mRNAs. These DDX1-containing vesicles protect essential transcripts from degradation and ensure their translation into proteins needed for cell survival. This work explains how cells maintain protein synthesis during stress conditions and has important implications for understanding chemotherapy resistance in cancer, neurodegenerative diseases where oxidative stress is prevalent, and normal aging processes.