GINS Complex Functions in Cancer Cell Proliferation

The GINS complex, composed of four subunits (PSF1, PSF2, PSF3 and SLD5), is an essential component of the eukaryotic replicative helicase, facilitating origin firing, DNA unwinding and fork progression. In cancer cells, aberrant expression or regulation of GINS subunits promotes uncontrolled proliferation by ensuring efficient DNA synthesis, coordinating cell cycle transitions and maintaining genomic integrity under replicative stress. Elevated levels of individual GINS components or of the intact complex correlate with poor prognosis in diverse malignancies, while genetic or epigenetic modulation of GINS expression alters tumour cell viability, triggers cell-cycle arrest and sensitises cells to apoptotic cues. The GINS complex also links replication dynamics to signalling pathways such as p53-GADD45A and MAPK/ERK, and contributes to the reactivation of quiescent, stem-like tumour cells within hypoxic niches. Collectively, these functions underscore the GINS complex as both a mechanistic linchpin of malignant proliferation and a candidate target for therapeutic intervention.

Research from Nature Portfolio

Recent studies have elucidated upstream regulatory circuits that govern GINS subunit expression and explored therapeutic avenues targeting PSF1. Investigations into microRNA-mediated control demonstrate that downregulation of miR-370 leads to SLD5 overexpression in bladder cancer cells, with interleukin-6 and DNA methyltransferase 1 forming a regulatory loop that suppresses miR-370 and drives tumour growth. Functional knockdown of SLD5 in xenograft models reduces tumour volume, emphasising its potential as a growth-inhibitory target. Separately, identification of an HLA-presented epitope derived from PSF1 has revealed immunogenic potential against stem-like cancer cells; vaccination with the PSF1 peptide elicits cytotoxic T-lymphocyte responses and interferon-γ production, suggesting a novel immunotherapeutic strategy to eradicate proliferative tumour populations.

GINS Complex Functions in Cancer Cell Proliferation publication trend

The graph below shows the total number of articles in gins complex functions in cancer cell proliferation across all publications each year (not limited to Nature Index journals).

Technical terms

GINS complex: A heterotetrameric assembly of PSF1, PSF2, PSF3 and SLD5 that forms part of the CMG helicase essential for DNA replication.

DNA replication fork: The fork-shaped region where parental DNA strands are separated and copied by the replisome.

Xenograft model: An in vivo system in which human tumour cells are implanted into immunodeficient mice to study cancer growth and therapy.

Apoptosis: Programmed cell death characterised by caspase activation, DNA fragmentation and membrane blebbing.

Prognostic biomarker: A molecular or cellular indicator that predicts disease outcome or patient survival, guiding clinical decision-making.

References

1. Regulation of SLD5 gene expression by miR-370 during acute growth of cancer cells. Scientific Reports (2016).
2. Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency. Scientific Reports (2017).
3. Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer. Brazilian Journal of Biology (2024).
4. Comprehensive analysis of GINS subunits prognostic value and ceRNA network in sarcoma. Frontiers in Cell and Developmental Biology (2022).
5. Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer. Bioscience Reports (2020).
6. GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. Journal of Cancer (2020).
7. Induced expression of GINS complex is an essential step for reactivation of quiescent stem-like tumor cells within the peri-necrotic niche in human glioblastoma. Journal of Cancer Research and Clinical Oncology (2018).