Tubulin α-1C chain as a central signalling hub in carcinogenesis: Towards a conceptual framework.

Tubulin α-1C chain (TUBA1C) is an α-tubulin isoform integral to the cytoskeletal microtubule network, maintaining cell shape, mechanical integrity, and intracellular transport. This review synthesises evidence from transcriptomic, functional, and clinical studies to present a unifying framework that positions TUBA1C as a signalling hub in cancer. Computational and experimental data demonstrate that TUBA1C is consistently overexpressed across multiple malignancies, including lung, glioma, gastric, colorectal, breast, renal, liver, pancreatic, and bladder cancers. Elevated TUBA1C expression correlates with advanced tumour stage, metastasis, chemoresistance, and poor patient survival, highlighting its active role in carcinogenesis beyond structural functions. Functional studies confirm that TUBA1C promotes cell-cycle progression via cyclin-CDK networks and EGFR-PI3K-AKT signalling, suppresses apoptosis through modulation of Bcl-2 family proteins and circTUBA1C-miR-143-3p interactions, and facilitates immune evasion by shaping an immunosuppressive tumour microenvironment. Moreover, TUBA1C enhances invasion and metastasis through PI3K-AKT and YAP pathways and drives metabolic reprogramming by linking cytoskeletal dynamics to YAP stabilisation and increased glycolytic flux. Collectively, these findings position TUBA1C as a central integrator of cytoskeletal organisation and oncogenic signalling. Recognising TUBA1C as a pan-cancer driver highlights its potential as a prognostic biomarker and therapeutic target, with implications for disrupting oncogenic circuits and improving precision oncology strategies.