The filopodial scaffold polyphosphate dictates cell adhesion-versus-invasion decisions
- 1University of Michigan
Abstract
Inorganic polyphosphate (polyP) is an ancient polymer conserved across all life, serving cell type and location specific functions in every major compartment. Yet its role at the plasma membrane, where it accumulates to peak levels in many primary cells, is largely unknown. Here we identify polyP as a stabilizing component of filopodia, actin based membrane protrusions that govern cell adhesion, contact inhibition, and chemotaxis. Elevating cellular polyP increases filopodial stability and enhances cell adhesion, whereas reducing polyP accelerates filopodial disassembly and promotes cell migration. Mechanistically, we find that polyP acts as a structural filopodial scaffold, recruiting and organizing IRSp53, a membrane curvature inducing protein. We show that metastatic fibroblasts and breast cancer organoids carry markedly reduced and intracellularly reorganized polyP levels relative to their non transformed counterparts. Restoring endogenous polyP via lipid nanoparticle delivery suppresses their invasive phenotypes and reverses prometastatic gene expression signatures, implicating polyP as a primordial tumor suppressor.
Related
- Multilayer and Biomimetic Polycaprolactone/Uterine ECM Scaffold for Uterine Tissue Engineering and Anti-Adhesion Barrier Applications via 3D-Printing Near-Field Melt Electrowriting
- A Saccharimonadia epibiont interacts with the polyphosphate-accumulating bacterium Candidatus Phosphoribacter in wastewater treatment plants
- Polyamines control inorganic polyphosphate levels during bacterial nitrogen starvation
- PFKFB3 inhibition dictates the adaptive responses and cell fates in tumor cells
- Platelets mediate fibrin-induced thromboinflammation and NETosis through a GPVI-polyphosphate-FXIIa procoagulant axis
BibTeX
@misc{rai2026filopodial,
title = {{The filopodial scaffold polyphosphate dictates cell adhesion-versus-invasion decisions}},
author = {A. Rai and A. Jain and H. Zunker and B. N. Obua and H. Ramchandani and J. Guan and A. Mousumi and Y. Xi and A. Erwin and P. Mahadevan and B. J. Oleson and A. B. Bardwell and J. Shoudis and J. Song and M. Suresh and S. Mosalaganti and A. P. Liu and J. West and U. Jakob},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.747915},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.747915v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The filopodial scaffold polyphosphate dictates cell adhesion-versus-invasion decisions
AU - A. Rai
AU - A. Jain
AU - H. Zunker
AU - B. N. Obua
AU - H. Ramchandani
AU - J. Guan
AU - A. Mousumi
AU - Y. Xi
AU - A. Erwin
AU - P. Mahadevan
AU - B. J. Oleson
AU - A. B. Bardwell
AU - J. Shoudis
AU - J. Song
AU - M. Suresh
AU - S. Mosalaganti
AU - A. P. Liu
AU - J. West
AU - U. Jakob
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.747915
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.747915v1
AB - Inorganic polyphosphate (polyP) is an ancient polymer conserved across all life, serving cell type and location specific functions in every major compartment. Yet its role at the plasma membrane, where it accumulates to peak levels in many primary cells, is largely unknown. Here we identify polyP as a stabilizing component of filopodia, actin based membrane protrusions that govern cell adhesion, contact inhibition, and chemotaxis. Elevating cellular polyP increases filopodial stability and enhances cell adhesion, whereas reducing polyP accelerates filopodial disassembly and promotes cell migration. Mechanistically, we find that polyP acts as a structural filopodial scaffold, recruiting and organizing IRSp53, a membrane curvature inducing protein. We show that metastatic fibroblasts and breast cancer organoids carry markedly reduced and intracellularly reorganized polyP levels relative to their non transformed counterparts. Restoring endogenous polyP via lipid nanoparticle delivery suppresses their invasive phenotypes and reverses prometastatic gene expression signatures, implicating polyP as a primordial tumor suppressor.
ER -