Cancerous cilia

Cilia (cilia) are microtubules that line the surface of some cells or tissues. They can be found on the mucous membrane of the nose, respiratory tract and lungs, as well as on the fallopian tubes and vas deferens in the female and male genital tract. They are able to move from side to side to remove microorganisms, various liquids or dead cells from the organs of the respiratory system and help transport sperm and egg through the organs of the reproductive system.

However, there are others similar to movable cilia – primary cilia. They are found on the surface of almost all cells of the body and have long been considered a rudimentary part of the cell. They are not constantly present, but from time to time they protrude from the centrosome – the part of the cell that divides it during division, appearing only at certain stages of the cell cycle.

The first data on the importance of primary cilia led to the discovery of a whole group of diseases based on a violation of their formation or function – ciliopathies. There are about 20 different ciliopathies, the prevalence of which is approximately 1 per 1000 people. These are serious and often disabling conditions affecting the systems of many organs. They can cause blindness, deafness, chronic respiratory infections, kidney disease, heart disease, infertility, obesity, diabetes and more. The symptoms and severity of ciliopathies vary widely, which makes it difficult to classify and diagnose them.

How can a malfunction of a small organelle, which was initially considered useless, lead to such a variety of serious and even sometimes fatal symptoms? It turned out that the cilia not only look like small antennas, but also act the same way. They contain proteins that "catch" signals from other cells or from the environment. These signals are then transmitted to the cell nucleus to activate the response.

Then began numerous studies of the structure and functions of cilia, associated proteins and the movement of these proteins to other parts of the cell, as well as factors directly or indirectly affecting this process. It became known that many of the signaling pathways regulated by cilia can stimulate the progression of cancer, and scientists began to look for patterns of the relationship between cilia and cancer.

Cilia, signals and cancer

Researchers have found that in many oncological diseases, including kidney, ovarian, prostate, breast and pancreatic cancers, malignant cells have a characteristic absence of primary cilia in contrast to healthy surrounding cells. Perhaps the loss of cilia is just a reaction to a violation of normal cellular regulation in cancer cells. But what if the loss of cilia is primary and it led to cancer?

Melanoma is one of the most aggressive types of tumors in humans. Some melanoma cells express quite high levels of the EZH2 protein, which suppresses the cilia genes, so malignant cells have fewer cilia. The loss of "antennas" activates some carcinogenic signaling pathways leading to the development of aggressive metastatic melanoma.

However, the loss of cilia does not always lead to the progression of cancer. Thus, in one type of pancreatic cancer, the presence, rather than the absence, of cilia correlates with an increase in metastasis and a decrease in patient survival.

Even with the same cancer, the picture is not the same. Medulloblastoma is the most common brain tumor in children, the growth of which is caused by the hedgehog signaling pathway regulated by cilia. This pathway is active during embryo development and inactive after birth. In many cancers, including medulloblastoma, hedgehog signaling is reactivated, and it can stimulate cancer growth. But studies of the effects of cilia in medulloblastoma have shown that cilia can both activate and protect against this tumor, depending on the way in which the hedgehog pathway is initially disrupted.

The discovery of such strong links between cilia and cancer interested researchers, they began searching for a cancer treatment aimed at this structure. One of the problems in the treatment of cancer is the formation of drug resistance. Many of these drugs are part of signaling pathways regulated by cilia, and scientists have found that blocking the growth of cilia in drug-resistant cancer cell lines can restore sensitivity to treatment.

Thus, the cilia, once considered a useless part of the cell remaining in the process of evolution, turned out to be an integral structure for understanding the mechanisms of cancer development and treatment. It is hoped that further studies of cilia will help unravel the complex tangle of relationships between them and tumors and provide both a new understanding of the factors that cause cancer and new goals for its treatment.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Conversation: Cilia: cell's long-overlooked antenna that can drive cancer – or stop it in its tracks.