Journal Article

DZNE-2026-00397

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intracellular complement Factor H promotes tumor progression through modulation of cell cycle and actin cytoskeleton.

Rezola Artero, M. ; Minery, A. ; Revel, M. ; Armento, A. ; Jarboui, M.-A. ; Boudhabhay, I. ; de Castro Deus, M. ; Zarantonello, A. ; Fleury, E. ; Segarra, L. ; Redissi, A. ; Merle, N. S. ; Dragon-Durey, M.-A. ; Monnot, C. ; Sautes-Fridman, C. ; Dimitrov, J. D. ; Fridman, W. H. ; Üffing, M.DZNE* ; Roumenina, L. T.

2026
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s42003-026-09807-4

Abstract: Overexpression of complement genes in the tumor microenvironment, including Factor H (FH), is a strong predictor of poor prognosis in multiple cancers. Its canonical functions in the bloodborne complement cascade, though, cannot explain this prognostic impact. Here, we demonstrate that FH operates within the intracellular space in fibroblasts and tumor cells. By transcriptomics approach in patient tumors, cellular and biochemical assays we revealed that the prognostic impact of FH overexpression is mediated mainly by its cell-intrinsic functions in tumor-promoting fibroblasts and malignant cells. Intranuclear FH interacts with the cell cycle-transcription factor E2F3. FH also promotes proliferation by lowering the nuclear p53 pool. Moreover, in ccRCC cancer cells, FH also regulates cytoskeleton organization and cell morphology, potentially, via interaction with the actin capping CapZ complex. Therefore, complement FH acts as a multitasking effector, regulating cell cycle and actin polymerization, challenging the paradigm of extracellular space-restricted functioning, considered for many complement proteins.

Keyword(s): Humans (MeSH) ; Actin Cytoskeleton: metabolism (MeSH) ; Cell Cycle (MeSH) ; Complement Factor H: metabolism (MeSH) ; Complement Factor H: genetics (MeSH) ; Cell Line, Tumor (MeSH) ; Disease Progression (MeSH) ; Cell Proliferation (MeSH) ; Tumor Microenvironment (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; Kidney Neoplasms: pathology (MeSH) ; Kidney Neoplasms: metabolism (MeSH) ; Kidney Neoplasms: genetics (MeSH) ; Complement Factor H ; CFH protein, human

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Contributing Institute(s):

1. Tübingen common (Tübingen common)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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