Tegavivint triggers TECR-dependent nonapoptotic cancer cell death.

Small molecules that induce nonapoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here we report that tegavivint, a drug candidate undergoing human clinical trials, can activate a unique mechanism of nonapoptotic cell death in sarcomas and other cancer cells. This lethal mechanism is distinct from ferroptosis, necroptosis and pyroptosis and requires the lipid metabolic enzyme trans-2,3-enoyl-CoA reductase (TECR).

ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway.

ENPP1 expression correlates with poor prognosis in many cancers, and we previously discovered that ENPP1 is the dominant hydrolase of extracellular cGAMP: a cancer-cell-produced immunotransmitter that activates the anticancer STING pathway. However, ENPP1 has other catalytic activities and the molecular and cellular mechanisms contributing to its tumorigenic effects remain unclear. Here, using single cell RNA-seq (scRNA-seq), we show that ENPP1 overexpression drives primary breast tumor growth and metastasis by synergistically dampening extracellular cGAMP-STING mediated antitumoral immunity and activating immunosuppressive extracellular adenosine (eADO) signaling.

Chemical Tuning of Fibers Drawn from Extensible Hyaluronic Acid Networks.

Polymer fibers with specific chemical and mechanical properties are key components of many biomaterials used for regenerative medicine and drug delivery. Here, we develop a bioinspired, low-energy process to produce mechanically tunable biopolymer fibers drawn from aqueous solutions. Hyaluronic acid (HA) forms dynamic cross-links with branched polyethylene glycol polymers end-functionalized with boronic acids of varied structure to produce extensible polymer networks.