The mTORC2 subunit RICTOR drives breast cancer progression by promoting ganglioside biosynthesis through transcriptional and epigenetic mechanisms.

ABSTRACT: Sphingolipid and ganglioside metabolic pathways are crucial components of cell signaling, having established roles in cancer cell proliferation, invasion, and migration. However, regulatory mechanisms controlling sphingolipid and ganglioside biosynthesis in mammalian cells are less known. Here, we show that RICTOR, the regulatory subunit of mTORC2, regulates the synthesis of sphingolipids and gangliosides in human luminal breast cancer-specific MCF-7 and BT-474 cells through transcriptional and epigenetic mechanisms. We observe that RICTOR regulates glucosylceramide levels by modulating the expression of UDP-Glucose Ceramide Glucosyl transferase (UGCG). We identify Zinc Finger protein X-linked (ZFX) as a RICTOR-responsive transcription factor whose recruitment to the UGCG promoter is regul

SUBMITTER: Ansari MN 

PROVIDER: S-EPMC12425323 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature