Work

In Silico Identification of Conserved ‘Fungal Islands’ in Human Septin9: Evidence for Atavistic Therapeutic Targets

Year: 2026

Type: article

Abstract: Metastasis, the primary cause of cancer mortality, relies on malignant cells acquiring extreme mobility and mechanical plasticity. We posit that this physical transition is driven not by de novo genetic innovations but by an atavistic reversion to highly conserved cytoskeletal blueprints, termed “Fungal Islands.” Through in silico sequence alignments and molecular docking, we investigated structural homology between human septin-9 (SEPT9) and its yeast ortholog, Cdc3. Our analysis reveals structural and thermodynamic parity within the G1/P-loop catalytic core across billions of years of eukaryotic divergence. This precise preservation of spatial configuration provides strong evidence against convergent evolution, demonstrating the core septin engine is constrained by intense purifying selection. Consequently, we argue that malignant cells exapt these functionally immutable ancestral nodes to drive a biomechanical shift, mirroring the invasive mechanics of fungal hyphal tips. This identifies a non-mutating structural template for next-generation ‘migrastatic’ therapies, offering a strategy to disable cancer’s migratory machinery while evading the mutational resistance typical of modern kinase inhibitors.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27135743

Authors: Ömer Eren Özcan, Ayhan Bilir, Berna Yıldırım

Institution: Atlas Üniversitesi

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499