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Updated: Mar 6, 2026
06:54
Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
Published on: June 15, 2019
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Intracellular complement Factor H promotes tumor progression through modulation of cell cycle and actin cytoskeleton
Mikel Rezola Artero1,2, Andrea Minery1, Margot Revel1
1Centre de Recherche des Cordeliers, Inflammation, Complement and Cancer team, Sorbonne Université, Inserm, Université Paris Cité, Paris, France.
Communications Biology
|March 4, 2026
Summary
Complement Factor H (FH) overexpression predicts poor cancer prognosis through intracellular functions. FH impacts cell cycle regulation and cytoskeleton organization, challenging its traditional extracellular role.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Overexpression of complement Factor H (FH) in the tumor microenvironment correlates with poor cancer prognosis.
- The canonical extracellular functions of FH in complement regulation do not fully explain its prognostic significance.
Purpose of the Study:
- To investigate the intracellular roles of FH in cancer progression.
- To elucidate the mechanisms by which FH overexpression impacts tumor-promoting fibroblasts and malignant cells.
Main Methods:
- Transcriptomics analysis of patient tumors.
- Cellular and biochemical assays.
- Investigation of FH interactions with nuclear and cytoplasmic proteins.
Main Results:
- FH was found to function intracellularly within fibroblasts and tumor cells.
- Intranuclear FH interacts with the cell cycle-transcription factor E2F3, promoting proliferation.
- FH lowers nuclear p53 levels, further contributing to proliferation.
- In ccRCC cells, FH regulates cytoskeleton organization and cell morphology, potentially via interaction with the CapZ complex.
Conclusions:
- Factor H exhibits cell-intrinsic functions that mediate its prognostic impact in cancer.
- FH acts as a multitasking effector, regulating cell cycle and actin polymerization.
- These findings challenge the paradigm of complement proteins functioning solely in the extracellular space.
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