How to stop cancer: attack on the microtubules

How to stop cancer: attack on the microtubules
Microtubules are rigid protein filaments that run through the inside of the cell. This is the main element of the cytoskeleton: microtubules separate chromosomes during cell division; coordinate the transport of molecules through the longest cells — neurons; a complex of microtubules — a core of flagella and cilia protruding outside the cell.

By structure, microtubules are hollow cylinders that are assembled from tubulin protein molecules. They are constantly rearranging: tubulin at one end joins while the other end of the microtubule disintegrates. Microtubule assembly is controlled by microtubule-associated proteins (MAPs). Microtubules are attached at one end to microtubule-organizing centers (MTOCs) such as centrosomes. In other words, centrosomes are the command post for microtubules.

In this review, you'll learn two ways that microtubules help cancer. Their research is helping to improve anti-cancer therapy.

Cell division and therapy against it

Microtubules are the main actors of cell division. During division, it is necessary to divide the genetic material of the mother cell between the daughter cells. Before dividing, the cell genome doubles, centrosomes diverge to opposite poles to end up in different cells after division. Microtubules separate the chromosomes and breed them to these poles with centrosomes — into new cells that are forming.
Microtubules move chromosomes through tubulin rearrangements. If you break the assembly or disassembly of the protein, then division will stop, because it does not make sense without the division of the genetic inheritance. This is how cancer therapy with tubulin inhibitors works [1]. These microtubule-binding chemicals stop cancer cells from dividing. Stopping division in the most uncomfortable position triggers cell death. So blocking the work of microtubules stops tumor growth.

Chemotherapy with tubulin inhibitors has been used since the 1960s. By themselves, such drugs are toxic to the body, because they disrupt the functioning of microtubules in all cells. But if tubulin inhibitors are targeted to cancer cells using special couriers, then the harm from drugs is leveled. Scientists continue to develop new drugs that, in addition, stop metastasis — the process of spreading tumors throughout the body [2, 3].

Cancer cells have special microtubules

Microtubules diverge throughout the cell, therefore they serve as routes for the transport of molecules within the cell. Like the autobahns, microtubules have road signs that regulate traffic — chemical modifications. After the synthesis of tubulin, the cell can change it for new needs and attach binding proteins to microtubules. Such modifications change the functioning of microtubules and transport throughout the cell [4]. This is often used by cancer cells [5].

Here are a few things that happen to microtubules in cancer cells due to chemical modifications:
* microtubules are more actively rearranged for the migration of cancer cells and stimulate metastasis, increase the invasiveness of metastases;
* microtubules protect cancer cells from death by preventing the transport of signaling molecules that trigger apoptosis;
* a strong modification of the microtubule protein makes cancer cells resistant to treatment with tubulin inhibitors.

It is necessary to continue to investigate microtubules in cancer cells in order to develop therapies that take into account tubulin modifications. To improve old treatments and create new ones, the Antimitotic Tubulin Library from ChemDiv can be useful to the researcher. This is a set of 18,000 components that will give you more freedom in scientific experiments.

Alexander Khazanov

References:

1. Čermák, Vladimír, et al. "Microtubule-targeting agents and their impact on cancer treatment." European journal of cell biology 99.4 (2020): 151075.
2. Zheng, Yiyan, et al. "Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation." Nature communications 9.1 (2018): 1-12.
3. Galmarini, Carlos M., et al. "Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells." BMC cancer 18.1 (2018): 1-13.
4. Janke, Carsten, and Maria M. Magiera. "The tubulin code and its role in controlling microtubule properties and functions." Nature Reviews Molecular Cell Biology 21.6 (2020): 307-326.
5. Wattanathamsan, Onsurang, and Varisa Pongrakhananon. "Post-translational modifications of tubulin: their role in cancers and the regulation of signaling molecules." Cancer Gene Therapy (2021): 1-8.
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