Prior studies have linked high blood cholesterol levels to various cancers, including colorectal cancers. However, it hasn’t been clear that lowering cholesterol can prevent colorectal cancers. Now, researchers at Weill Cornell Medicine have found in mice hard-to-detect colorectal pre-cancerous lesions known as serrated polyps, and the aggressive tumors that develop from them, depend heavily on the ramped-up production of cholesterol. Their finding points to the possibility of using cholesterol-lowering drugs to prevent or treat such tumors.

The findings are published in Nature Communications in an article titled, “Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.”

“The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown,” the researchers wrote. “Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis.”

A University of Oxford-led study has found that diverse communities of resident commensal gut bacteria collectively protect the human gut from disease-causing microorganisms by consuming the nutrients that the pathogen would need to be able to gain a foothold in the host.

The team used an ecological approach to investigate how colonization by two major bacterial pathogens— Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium (S. Typhimurium)—is influenced by a range of human gut bacteria both in vitro and in gnotobiotic mice. They found that the ecological diversity of the microbiome was important for colonization resistance. While single species of gut microbiota alone had negligible effects on providing effective resistance to pathogens, certain combinations of essential key species within diverse communities exhibited much greater colonization resistance when together.

Having found that these communities block pathogen growth by consuming nutrients that would be required by the pathogen, the team also showed that the concept of nutrient blocking can be used to predict specific sets of commensal microbiota that will resist a novel bacterial pathogen, using genome sequence data alone.

Researchers at Shanghai Jiao Tong University School of Medicine, China, have discovered that shutting down part of the innate immune system increases anti-tumor activity.

In a paper, “Noncanonical MAVS signaling restrains dendritic cell–driven antitumor immunity by inhibiting IL-12,” published in Science Immunology, the team details how exploring the role of mitochondrial antiviral signaling in tumor immunity uncovered unexpected insights into the relationship with immune responses and potential therapeutic implications.

Mitochondrial antiviral-signaling (MAVS) proteins are part of the innate immune system encoded by the nuclear genome found mainly on the mitochondrial outer membrane. Considered a first line of defense against viral infections, they are rapidly produced upon viral recognition and quickly reduced when a virus is cleared from the system.