C1q Receptor Interactions in Cancer Biology

The complement component C1q, a multimeric recognition molecule of the innate immune system, engages with a range of cellular receptors to influence tumour development and progression. Key receptors include the globular head receptor gC1qR and the collagen tail receptor cC1qR, as well as the intracellular and cell‐surface associated binding protein C1QBP (also known as p32). These interactions occur within the tumour microenvironment, where C1q–receptor binding shapes inflammatory responses, modulates angiogenesis and alters extracellular matrix remodelling. Beyond direct effects on cancer cell survival and proliferation, C1q–receptor crosstalk can suppress cytotoxic T-cell functions by mechanisms analogous to established immune checkpoints. Dysregulation of C1q receptor expression is observed across multiple malignancies, where it correlates with enhanced metastatic potential, therapy resistance and poor prognosis. The functional versatility of C1q receptors renders them both biomarkers of disease state and candidate targets for novel immunomodulatory and anti-metastatic therapies.

Research from Nature Portfolio

Recent studies have demonstrated that C1QBP expression restrains metastatic dissemination in renal cell carcinoma. Loss of C1QBP led to upregulation of the GSK3/β-catenin/L1CAM signalling axis, resulting in enhanced cell adhesion, invasion and distant metastasis in vivo. Restoration of C1QBP reversed these effects, indicating its role as a negative regulator of metastatic programmes. These findings highlight a tissue-specific mechanism by which a C1q-binding protein can suppress tumour spread and suggest that modulation of C1QBP levels may represent a therapeutic strategy to limit renal carcinoma progression.

C1q Receptor Interactions in Cancer Biology publication trend

The graph below shows the total number of articles in c1q receptor interactions in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Complement C1q: A multimeric protein that initiates the classical complement pathway and recognises altered self and non-self targets.

gC1qR: A multifunctional receptor for the globular head domains of C1q, also known as p33, implicated in immune modulation and cell adhesion.

C1QBP (p32): A mitochondrial and cell-surface protein that binds the collagen tail of C1q and participates in signalling networks affecting cell proliferation and survival.

Tumour microenvironment: The complex milieu of stromal cells, immune cells, extracellular matrix and soluble factors surrounding a tumour.

Angiogenesis: The formation of new blood vessels from existing vasculature, crucial for tumour growth and metastasis.

Metastasis: The process by which cancer cells spread from the primary site to establish secondary tumours in distant organs.

References

1. The C1q and gC1qR axis as a novel checkpoint inhibitor in cancer. Frontiers in Immunology (2024).
2. C1QBP Mediates Breast Cancer Cell Proliferation and Growth via Multiple Potential Signalling Pathways. International Journal of Molecular Sciences (2023).
3. Multi-functional, multicompartmental hyaluronan-binding protein 1 (HABP1/p32/gC1qR): implication in cancer progression and metastasis. Oncotarget (2018).
4. C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells. Scientific Reports (2017).