Tubulin critical role in cancer development

Tubulin, a globular protein, plays a critical role in the development and treatment of cancer. It forms microtubules, which are essential components of the cell's cytoskeleton, involved in various cellular processes including cell division, intracellular transport, and the maintenance of cell shape . In cancer cells, the dynamics of tubulin polymerization and the formation of mitotic spindles are key targets for chemotherapy agents
Tubulin and Cancer Progression The expression of specific tubulin isotypes, such as class III ß-tubulin (TUBB3), has been associated with aggressive tumor features and advanced tumor infiltration . These isotypes can confer resistance to a wide range of drug classes in both solid and hematological tumors . Moreover, tubulin isotypes have been implicated in defining the niche of cancer stem cells (CSCs), influencing properties such as drug resistance, metastasis, and immune evasion
Microtubule-Associated Proteins (MAPs) and Metastasis
MAPs are integral to the regulation of microtubule dynamics and have been shown to play a role in cancer aggressiveness, particularly in metastasis . They are considered fundamental regulators that contribute to cancer cell migration, invasion, and epithelial-to-mesenchymal transition
. This makes MAPs potential therapeutic targets and prognostic markers for cancer management.
Tubulin-Targeting Anticancer Agents
A variety of agents target tubulin to disrupt cancer cell division. These include taxanes, vinca alkaloids, colchicine, and podophyllotoxin, each with a unique mechanism of action on microtubule dynamics . Microtubule-targeting agents (MTAs) are considered highly promising in cancer treatment due to their ability to inhibit tubulin polymerization, induce mitotic spindle arrest, and ultimately lead to cancer cell death
Tubulin Isotypes and Chemotherapy Resistance
Alterations in tubulin isotype expression can modulate cancer biology and influence chemotherapy resistance . The presence of specific isotypes can affect the prognosis and treatment response in different cancers, making them important factors in the development of targeted therapies
Autophagy and Tubulin-Modifying Enzymes
Tubulin-modifying enzymes play a role in cancer autophagy, which is a process that can either promote or inhibit cancer progression . The crosstalk between autophagy and microtubules presents a potential target for controlling cancer growth
Tubulin in Pancreatic Cancer
In pancreatic ductal adenocarcinoma (PDAC), microtubules are significantly involved in the disease's progression, making them a core approach in targeted therapy . Agents that inhibit microtubule polymerization, known as microtubule-depolymerizing agents (MDAs), and microtubule-stabilizing agents (MSAs) are used to treat various types of cancer, including PDAC
Novel Tubulin-Targeting Compounds New compounds, such as Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC), have shown potential in targeting tubulin polymerization and inducing mitotic blockage in cancer cells. MBIC has demonstrated greater toxicity against cancer cells compared to normal cells and has shown synergistic effects with conventional drugs, potentially reducing toxicity and drug resistance
In summary, tubulin and its associated proteins are central to the progression and treatment of cancer. Understanding the role of tubulin isotypes and MAPs in cancer can lead to the development of more effective therapies that target these proteins. The ongoing research into tubulin-targeting agents and their mechanisms offers hope for improved cancer treatments and outcomes.