Microenvironmental factors originating from RAS-mutated cancer stem cells stimulated an angiogenic feedback loop with the surrounding environment causing the expression of leptin and TGF-β receptors on the cancer stem cells. Most significantly, leptin and TGF-β signaling were required for malignant transformation.

The findings, which were published in the Nov. 30, 2022 issue of Nature, raise “the intriguing possibility that many cancer mutations may function to lock into place, rather than set the course of, a path that is predetermined by aberrant crosstalk between a cancer stem cell and its microenvironment,” said senior author Elaine Fuchs, Rebecca C. Lancefield Professor and Howard Hughes Medical Institute investigator at Rockefeller University.