The nuclear phosphoinositide-p53 signalosome in the regulation of cell motility

Dysregulation of p53 and phosphoinositide (PIP_n) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIP_n-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIP_n signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIP_ns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIP_ns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIP_n-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.