TUBB3 encodes the neuronal-specific β-tubulin isotype III, a component of neuronal microtubules. Microtubules regulated by TUBB3 play crucial roles in neuronal migration, axon growth and guidance, which are essential for the normal development and function of the nervous system [1]. It may also be involved in some signaling pathways related to cancer cell behaviors, though the exact pathways are still being explored. Genetic models, such as gene knockout mouse models, can be valuable to study its function.

In in vitro and mouse models, loss-of-function and missense variants of TUBB3 can alter microtubule dynamics and microtubule-kinesin interactions, causing errors in cranial and central axon growth, guidance, and cortical neuronal migration [1]. In prostate cancer, TUBB3 knockdown using siRNA-loaded bone-targeting lipid nanoparticles significantly attenuates bone metastasis in vivo, and also reverses resistance to docetaxel and cabazitaxel, and cross-resistance between them [2,3]. In gallbladder cancer, TUBB3 knockdown inhibits cell proliferation, migration, and invasion both in vitro and in a xenograft mouse model, and affects the Akt/mTOR signal pathway [4].

In conclusion, TUBB3 is essential for neuronal development through its role in microtubule-related functions. Research using KO/CKO mouse models has revealed its significance in diseases like neurodevelopmental disorders and multiple cancers, such as prostate and gallbladder cancers. Understanding TUBB3 function provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Puri, Dharmendra, Barry, Brenda J, Engle, Elizabeth C. 2023. TUBB3 and KIF21A in neurodevelopment and disease. In Frontiers in neuroscience, 17, 1226181. doi:10.3389/fnins.2023.1226181. https://pubmed.ncbi.nlm.nih.gov/37600020/

2. Dong, Bingqi, Gu, Yanlun, Sun, Xiaojiao, Pang, Xiaocong, Cui, Yimin. 2024. Targeting TUBB3 Suppresses Anoikis Resistance and Bone Metastasis in Prostate Cancer. In Advanced healthcare materials, 13, e2400673. doi:10.1002/adhm.202400673. https://pubmed.ncbi.nlm.nih.gov/38809199/

3. Sekino, Yohei, Han, Xiangrui, Kawaguchi, Takafumi, Yasui, Wataru, Matsubara, Akio. 2019. TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer. In International journal of molecular sciences, 20, . doi:10.3390/ijms20163936. https://pubmed.ncbi.nlm.nih.gov/31412591/

4. Liu, Zijun, Li, Suqin, Dong, Jianning, Miao, Yi. . TUBB3 Promotes Growth and Invasion of Gallbladder Cancer Cells by Akt/mTOR Signal Pathway. In Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, 40, 23-33. doi:10.1615/JEnvironPatholToxicolOncol.2021036821. https://pubmed.ncbi.nlm.nih.gov/33822514/