GTSE1 in Cancer Progression: From Mitotic Regulator to Therapeutic Target

Cancer progression depends on unchecked proliferation, genomic instability, and metastatic dissemination. G2 and S phase-expressed protein 1 (GTSE1), a microtubule-associated protein encoded on chromosome 22q13.31, was originally characterized as a cell-cycle-regulated regulator of p53 and has since emerged as a cancer-associated protein elevated in multiple malignancies. This narrative review, supported by a structured assessment of the primary literature, examines the mechanistic and clinical evidence linking GTSE1 to tumour progression. GTSE1 operates through three mechanistically distinct but interrelated routes: regulation of mitotic spindle microtubule dynamics and chromosomal stability; suppression of p53-dependent apoptosis; and promotion of epithelial–mesenchymal transition programmes that drive migration, invasion, and metastasis. Its abundance is additionally controlled by transcriptional programmes, phosphorylation-dependent protein stabilization, and non-coding RNA and epitranscriptomic mechanisms. Clinically, elevated GTSE1 expression is associated with adverse outcomes across multiple tumour types, although the evidence remains predominantly retrospective and prospective validation is lacking. We address the apparent discrepancy between reported effects of GTSE1 on spindle microtubule dynamics and assess the relationship between GTSE1 and CDK4/6 inhibition as a clinically testable hypothesis. The principal challenge is not a lack of proposed mechanisms, but the uneven quality and limited independent replication of the available evidence.