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Phosphoinositide signalling in cell motility and adhesion

Nature Cell Biology volume 27, pages 736–748 (2025)Cite this article

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Abstract

Cell motility and adhesion are fundamental components for diverse physiological functions, including embryonic development, immune responses and tissue repair. Dysregulation of these processes can lead to a range of diseases, including cancer. Cell motility and adhesion are complex and often require regulation by an intricate network of signalling pathways, with phosphatidylinositol phosphates (PIPs) having a central role. PIPs are derived from phosphatidylinositol phosphorylation and are instrumental in mediating membrane dynamics, intracellular trafficking, cytoskeletal organization and signal transduction, all of which are crucial for cellular responses to environmental stimuli. Here we discuss the mechanisms through which PIPs modulate cell motility and adhesion by examining their roles at focal adhesions, within the cytoskeleton, at protein scaffolds and in the nucleus. By providing a comprehensive overview of PIP signalling, this Review underscores their significance in maintaining cellular homeostasis and highlights their potential as therapeutic targets in diseases characterized by aberrant cell motility and adhesion.

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Fig. 1: Overview of PIP metabolism and PI3K–AKT signalling with relevance for cell motility and adhesion.
Fig. 2: Regulation of FA dynamics by PIPs and associated proteins.
Fig. 3: Role of PIP signalling in microtubule dynamics.
Fig. 4: IQGAP1-mediated regulation of cell dynamics via PIP signalling.
Fig. 5: Role of nuclear PIPs and their associated factors.

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Acknowledgements

M.C. is supported by grants from the National Natural Science Foundation of China (32400577), Guangdong Basic and Applied Basic Research Foundation (2023A1515110237), Shenzhen Medical Research Fund (D2301007), Shenzhen Natural Science Foundation (JCYJ20240813094605008) and Medical Research Innovation Project (G030410001). J.S. is supported by grants from the National Natural Science Foundation of China (82071193), Guangdong Zhujiang Program (0920220233) and Science and Technology Foundation of Shenzhen (RCYX20210706092040044 and JCYJ20220818102611025). This work was supported in part by National Institutes of Health grants (R35GM134955 to R.A.A. and R01CA286492 to R.A.A. and V.L.C.), Department of Defense Breast Cancer Research Program grants (W81XWH-17-1-0258 and HT9425-23-1-0554 to R.A.A. and W81XWH-17-1-0259, W81XWH-21-1-0129 and HT9425-23-1-0553 to V.L.C.) and a grant from the Breast Cancer Research Foundation (to V.L.C.).

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Authors and Affiliations

  1. Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, China

    Xiaoting Hou, Chang Ren, Jing Jin, Yu Chen, Xinyu Lyu, Kangle Bi, Jichao Sun & Mo Chen

  2. SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China

    Xiaoting Hou, Chang Ren, Yu Chen, Kangle Bi & Mo Chen

  3. Department of Critical Care Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College at Jinan University and The First Affiliated Hospital at the Southern University of Science and Technology), Shenzhen, China

    Jing Jin & Jichao Sun

  4. Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People’s Hospital, Shenzhen, China

    Jing Jin & Jichao Sun

  5. Department of Medicine, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA

    Noah D. Carrillo & Vincent L. Cryns

  6. University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA

    Vincent L. Cryns & Richard A. Anderson

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  1. Xiaoting Hou
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  2. Chang Ren
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  11. Mo Chen
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Contributions

X.H., C.R., J.J., X.L., J.S. and M.C. drafted the manuscript. X.H., Y.C., K.B., N.D.C., R.A.A., V.L.C., J.S. and M.C. edited the manuscript. X.H., C.R., J.J., X.L., Y.C., K.B., N.D.C., J.S. and M.C. visualized the data. R.A.A., V.L.C., J.S. and M.C. acquired funding. J.S. and M.C. supervised the project.

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Correspondence to Jichao Sun or Mo Chen.

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Hou, X., Ren, C., Jin, J. et al. Phosphoinositide signalling in cell motility and adhesion. Nat Cell Biol 27, 736–748 (2025). https://doi.org/10.1038/s41556-025-01647-4

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