神经酰胺合成通过YAP驱动的再生程序介导结直肠癌转移

INTRODUCTION: Metastasis accounts for most colorectal cancer (CRC)–related deaths, yet the mechanisms by which primary tumor cells acquire metastatic capability remain poorly understood. Whereas genetic mutations drive tumor initiation, CRC stem cells transition between distinct cellular states, displaying phenotypic plasticity that drives disease progression. Tumor cells can shift from a conventional intestinal stem cell state to a yes-associated protein (YAP)–driven regenerative or fetal-like state associated with tissue repair. Intestinal cell states are shaped by intrinsic and environmental cues. Among these, diet is an established modifier of CRC risk. High-fat feeding expands the intestinal stem cell pool and confers tumor-initiating capacity on progenitors, indicating that dietary lipids act directly on the cell states from which tumors arise. …