A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages.

Building a complex for destruction.

Ranes et al. (2021) report on an in vitro reconstituted β-catenin destruction complex and elucidate the contributions of full-length and cancer-related mutated core components to β-catenin turnover, thereby advancing our understanding of the inner workings of this tumor suppressor complex.

Modulation of the secretory pathway by amino-acid starvation.

As a major anabolic pathway, the secretory pathway needs to adapt to the demands of the surrounding environment and responds to different exogenous signals and stimuli. In this context, the transport in the early secretory pathway from the endoplasmic reticulum (ER) to the Golgi apparatus appears particularly regulated. For instance, protein export from the ER is critically stimulated by growth factors.