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

Xiaoting HOU; Yu CHEN; Bo ZHOU; Fengting LIU; Lingyun DAI; Chunbo CHEN; Noah D CARRILLO; Vincent L CRYNS; Richard A ANDERSON; Jichao SUN; Mo CHEN

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

Author: Xiaoting HOU ¹ ; Yu CHEN ¹ ; Bo ZHOU ¹ ; Fengting LIU ¹ ; Lingyun DAI ¹ ; Chunbo CHEN ¹ ; Noah D CARRILLO ² ; Vincent L CRYNS ² ; Richard A ANDERSON ³ ; Jichao SUN ¹ ; Mo CHEN ¹
Author Information

1. Department of Critical Care Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China.
2. Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, United States.
3. University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, United States.
Publication Type:Review
Keywords: cell motility; nucleus; p53; phosphoinositide; signalosome
MeSH: Humans; Tumor Suppressor Protein p53/metabolism*; Signal Transduction; Cell Movement; Cell Nucleus/metabolism*; Phosphatidylinositols/metabolism*; Proto-Oncogene Proteins c-akt/metabolism*; Animals; Neoplasms/pathology*; Phosphatidylinositol 3-Kinases/metabolism*
From: Protein & Cell 2025;16(10):840-857
CountryChina
Language:English
Abstract: Dysregulation of p53 and phosphoinositide (PIPn) 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 PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns 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 PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.