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Target: TUBB6


Research on TUBB6

1. Target Summary:

TUBB6, or Tubulin Beta-6 Class V, is a member of the tubulin family, which is essential for microtubule formation and dynamics. It plays a critical role in various cellular processes, including cell division, intracellular transport, and maintaining cell shape. TUBB6 has been implicated in several diseases, particularly in cancer, where its expression levels correlate with tumor aggressiveness and patient prognosis.

2. Mechanism:

TUBB6 contributes to the assembly and stability of microtubules, which are crucial components of the cytoskeleton. Microtubules are dynamic structures that undergo constant polymerization and depolymerization, a process regulated by various tubulin isotypes, including TUBB6.
  • Microtubule Dynamics: TUBB6 is involved in the regulation of microtubule dynamics, influencing cellular processes such as mitosis and intracellular transport. It has been shown to control both microtubule and actin dynamics in osteoclasts, which are cells responsible for bone resorption (Maurin et al., 2021, PMID: 34869381).
  • Angiogenesis: TUBB6 is upregulated in conditions such as oxygen-induced retinopathy and is linked to the WNT signaling pathway, which is crucial for angiogenesis (Zhang et al., 2025, PMID: 40083923). The YBX1 protein regulates TUBB6 expression by binding to its mRNA, enhancing its stability and promoting angiogenic processes.
  • Cancer Progression: In cancer, TUBB6 expression is associated with aggressive tumor behavior. For instance, in muscle-invasive bladder cancer, TUBB6 has been identified as a biomarker for poor prognosis (Kim et al., 2023, PMID: 36054443). Its overexpression can disrupt microtubule stability, leading to increased cell migration and invasion.

3. Approved Drugs:

As of now, there are no specific drugs approved that target TUBB6 directly. However, its role in microtubule dynamics suggests potential therapeutic avenues, particularly in cancer treatment where microtubule-targeting agents (like taxanes) are used.

4. Hypotheses:

  • Tumor Biomarker: TUBB6 may serve as a reliable biomarker for predicting outcomes in various cancers, particularly in muscle-invasive bladder cancer and glioblastoma (Jiang et al., 2020, PMID: 33193654).
  • Therapeutic Target: Targeting TUBB6 could provide therapeutic benefits in diseases characterized by abnormal angiogenesis or cell proliferation, such as cancer (Zhang et al., 2025, PMID: 40083923).
  • Role in Muscle Disorders: Given its involvement in muscle regeneration, modulation of TUBB6 expression may influence outcomes in muscular dystrophies (Randazzo et al., 2019, PMID: 30535187).

5. Validation:

  • Prognostic Value: Studies have validated TUBB6 as a prognostic biomarker in multiple cancers, showing correlations with disease severity and patient outcomes (Kim et al., 2023, PMID: 36054443; Jiang et al., 2020, PMID: 33193654).
  • Functional Studies: Experimental studies have demonstrated that silencing TUBB6 reduces angiogenic capabilities in vitro and in vivo, supporting its role in promoting tumor growth and metastasis (Zhang et al., 2025, PMID: 40083923).

6. Clinical Trials:

While specific clinical trials targeting TUBB6 directly are limited, its role as a biomarker has opened avenues for trials assessing the efficacy of antiandrogens in colorectal cancer (Mariani et al., 2012, PMID: 22438565). The ENDCAP-C study is validating biomarkers, including TUBB6, for detecting dysplasia in ulcerative colitis (Beggs et al., 2019, PMID: 30473377).

7. Involved Pathways:

  • WNT Signaling Pathway: TUBB6 is linked to the WNT signaling pathway, which is crucial for cell proliferation and differentiation (Zhang et al., 2025, PMID: 40083923).
  • Angiogenesis: TUBB6 plays a significant role in angiogenesis, particularly in pathological conditions like diabetic retinopathy (Zhang et al., 2025, PMID: 40083923).

8. Associated Genes:

TUBB6 interacts with several hub genes, including ANXA2, S100A11, FLNA, and MSN, which are involved in cancer progression and prognosis (Jiang et al., 2020, PMID: 33193654).

9. Target Expression:

TUBB6 is expressed in various tissues, with elevated levels observed in cancerous tissues compared to normal tissues. Its expression is particularly high in endothelial cells and is associated with proliferative states in tumors (Kim et al., 2023, PMID: 36054443).

10. Additional Context:

The dysregulation of TUBB6 has implications not only in cancer but also in muscle disorders and ocular diseases. Its role in microtubule dynamics makes it a critical target for understanding various pathologies.

11. References:

  • Zhang, Y. R., Li, W. Q., & Zhang, Z. H. (2025). YBX1-driven TUBB6 upregulation facilitates ocular angiogenesis via WNT3A-FZD8 pathway. Theranostics. PMID: 40083923.
  • Maurin, J., Morel, A., & Guerit, D. (2021). The Beta-Tubulin Isotype TUBB6 Controls Microtubule and Actin Dynamics in Osteoclasts. Frontiers in Cell and Developmental Biology. PMID: 34869381.
  • Kim, B., Jung, M., & Moon, K. C. (2023). Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer. International Journal of Cancer. PMID: 36054443.
  • Randazzo, D., Khalique, U., & Belanto, J. J. (2019). Persistent upregulation of the beta-tubulin tubb6, linked to muscle regeneration, is a source of microtubule disorganization in dystrophic muscle. Human Molecular Genetics. PMID: 30535187.
  • Jiang, L., Zhu, X., & Yang, H. (2020). Bioinformatics Analysis Discovers Microtubular Tubulin Beta 6 Class V (TUBB6) as a Potential Therapeutic Target in Glioblastoma. Frontiers in Genetics. PMID: 33193654.
  • Mariani, M., Zannoni, G. F., & Sioletic, S. (2012). Gender influences the class III and V beta-tubulin ability to predict poor outcome in colorectal cancer. Clinical Cancer Research. PMID: 22438565.
  • Beggs, A. D., Mehta, S., & Deeks, J. J. (2019). Validation of epigenetic markers to identify colitis associated cancer: Results of module 1 of the ENDCAP-C study. EBioMedicine. PMID: 30473377.