Review Paper:
The Contribution
of DNA Replication and Cell Cycle Genes in promoting Metastasis
Vardhan Nalla Reddy Harsha, Preetha K., Radhu L. and Reddy Aluru Ranganadha
Res. J. Biotech.; Vol. 21(2); 335-345;
doi: https://doi.org/10.25303/212rjbt3350345; (2026)
Abstract
Metastasis, the dissemination of cancer cells to remote organs, is the primary cause
of cancer-related mortality and is governed by complex disturbances in DNA replication
and cell cycle regulation. This research identifies nine pivotal genes: CDC45, MCM5,
ASF1B, RFC4, E2F1, TK1, CHTF18, CENPM and CDCA3, that are persistently overexpressed
in metastatic tumours and significantly correlated with unfavourable clinical outcomes.
CDC45 and MCM5 are essential constituents of CMG helicase complex that promotes
the initiation of replication origins; their overexpression triggers replication
stress and activates pro-metastatic signalling pathways. E2F1, a key transcriptional
regulator, modulates the expression of several other metastasis-associated genes
including CDCA3, TK1, RFC4, ASF1B and CENPM. The dysregulation of these downstream
pathways facilitates epithelial–mesenchymal transition (EMT), genomic instability
and the preservation of cancer stem cell-like characteristics.
CHTF18 is pivotal in maintaining sister chromatid cohesion and facilitating tolerance
to replication stress, both of which are vital for genomic integrity during accelerated
cancer cell proliferation. Pan-cancer expression profiling underscores the collective
prognostic and biomarker potential of these genes, with multigene analysis providing
superior predictive value compared to individual indicators. Emerging therapeutic
strategies targeting replication-associated pathways, such as inhibition of CMG
helicase, ATR/CHK1 signaling and gene-specific inhibitors of RFC4, ASF1B and CDCA3,
show promise but are challenged by tumor heterogeneity and drug resistance. Future
advances in single-cell genomics, structural biology and liquid biopsy technologies
are expected to facilitate more precise and effective interventions against metastatic
cancer.
