Vincent, F. | Search bioRxiv

bioRxiv2021

Sortilin exhibits tumor suppressor-like activity by limiting EGFR transducing function

Lung cancer is the leading cause of cancer deaths worldwide and remains one of the most incurable. Tyrosine kinase receptors, such as the epidermal growth factor receptor (EGFR), are often aberrantly activated and drive tumor growth. Monotherapy with tyrosine kinase inhibitors to deactivate EGFR has shown initial efficacy, but their benefits tend to decline over time. EGFR acts as a transcriptional factor promoting the expression of co-oncogenic drivers, which, in turn, interact with canonical EGFR mutations to induce therapeutic relapse. This study reports that sortilin, a crucial regulator of cytoplasmic EGFR, attenuates its transducing function. Genome-wide chromatin binding revealed that sortilin interacts with gene regulatory elements occupied by EGFR. These results suggest a model, in which sortilin exhibits potential tumor suppressor-like activity by concurrently binding to regulatory elements of cMYC. Sortilin expression in lung adenocarcinoma may be predictive of the efficacy of anti-EGFR strategies.

cancer biology↗

bioRxiv2020

Viral infection of algal blooms leaves a halogenated footprint on the dissolved organic matter in the ocean

Algal blooms are important hotspots of primary production in the ocean, forming the basis of the marine food web and fueling the pool of dissolved organic matter (DOM)1, which is the largest global inventory of reduced carbon and a market place for metabolic exchange in the ocean2. Marine viruses are key players in controlling algal bloom demise and act as major biogeochemical drivers of nutrient cycling and metabolic fluxes by shunting algal biomass from higher trophic levels to the DOM pool, a process termed the viral shunt3,4. Nevertheless, the metabolic composition of virus-induced DOM (vDOM) in the marine environment is unknown. To decode the metabolic footprint of the viral shunt, we induced a bloom of the ecologically important alga Emiliania huxleyi in the natural environment, and followed its succession using an untargeted exometabolomics approach. Here we show that algal bloom succession induces extensive and dynamic changes in the exometabolic landscape, especially during bloom demise. By correlating to a specific viral gene marker, we discovered a set of novel chlorine-iodine-containing metabolites that were induced by viral infection and copiously released during bloom demise. We further detected several of these chloro-iodo metabolites in virus-infected open ocean blooms of E. huxleyi, supporting their use as sensitive biomarkers for virus-induced demise in the natural environment. Therefore, we propose halogenation to be a hallmark of the E. huxleyi vDOM, providing insights into the profound metabolic consequences of viral infection for the marine DOM pool.

microbiology↗