2021-10-27 10:32:58
This week we are going to remember the inauguration, almost 20 years ago, of the National Center for Oncological Research, the CNIOand we are going to talk about one of the genes most frequently involved in the development of cancer, the Kras gene, so called because it was identified in the genome of the sarcoma virus, discovered by the German scientist Werner H. Kirsten.
A sarcoma is a malignant tumor that arises from the tumor transformation of mesenchyme cells, that is, cells of the connective tissue of the organism. This tissue is one of the four tissues of organisms, along with epithelial, nervous, and muscle tissue. Connective tissue is located between these tissues, helping their connection and organization. Well, connective tissue cells, like those of others, can become cancerous and cause tumors called sarcomas.
The Kras gene, when it mutates in certain places of its sequence of letters, produces a protein, also called KRAS, but with capital letters, which is activated all the time. This activation sends a constant signal inside the cell indicating that the cell should reproduce. This, along with other processes that also involve genetic changes, can eventually cause cancer. It doesn’t always cause it, because sometimes the immune system can prevent it.
The Kras gene is one of the most frequently mutated, not only in sarcomas, but in other more frequent types of tumors, including colon and lung tumors, but also pancreatic and ovarian tumors. Let’s see what he had to say about this gene on the occasion of the inauguration of the National Cancer Research Center, and then, as always, briefly analyze where we are today on this research topic.
Read the article The maintenance of cancer
Has the promise of the research results of Dr. Varmus’s team come true? If not all have been met, I dare say, numerous research teams around the world continue to work apace to make them fully a reality.
But before we get into the new antitumor therapies that try to block the activity of the protein KRAS, I think it is convenient to explain how this protein works and why some mutations in the gene that produces it contribute to the development of cancer. Understanding its mode of operation will, in turn, allow us to understand the operation of some of the antitumor therapies that seek to block the operation of this protein, which is necessary for tumors to continue growing, as demonstrated by the work of Dr. Varmus’ team, that he recounted before.
The protein KRAS It works like a switch that, once turned on after receiving a signal, stays on for a while and then turns off. The signal is usually a growth factor, something that tells the cell that receives it to reproduce. Once this signal has performed its function, KRAS it turns off and the daughter cells generated in the reproduction of its progenitor do not continue reproducing in turn, but rather wait for new signals that induce them to do so. If these do not arrive, cell reproduction will stop.
How does this switch work? Like all switches, when the protein KRAS receives an inducer signal, it changes its state from off to on. The off state of the protein KRAS It is maintained by the binding of a molecule. This molecule must be detached from KRAS so that it can be turned on. What molecule is it? Well, it is nothing less than one of those found in the ADNthe molecule called GDPguanosine diphosphate.
The prefix “di” in the word “diphosphate” indicates that the molecule possesses two phosphate groups. This group is formed by a phosphorus atom surrounded by four oxygen atoms, and it is the one that serves as a bridge for the union of the millions of different letters that form the ADN. However, when the letters of the ADN are separated from it, they can have two or three of these phosphate groups attached. Thus we have, for example, adenosine diphosphate, ADPand adenosine triphosphate, the ATPderivatives of adenosine, the letter A of the ADN. These are famous molecules because they are the currency of energy exchange in cells. In addition to A, the other letters of the ADN They can also join two or three phosphate groups, although only when they are separated and not part of the group. ADN. In particular, guanosine, the molecule with the letter G, can form guanosine diphosphate and guanosine triphosphate, called GDP y GTPrespectively.
Just like the molecules ADP y ATP serve for energy exchanges in metabolic reactions of cells, molecules GDP y GTPAlthough they can also store and release metabolic energy, they also serve, and in a very important way, to turn on or off some molecules that function as on/off switches for certain cellular processes. One of those molecules is protein. KRAS.
This protein is attached to the inside of the cell membrane, in an off state, waiting to receive some external signal that can turn it on. This signal may be a growth factor that interacts with a detector on the cell membrane. If this signal arrives, the protein will turn on and trigger a biochemical process that will drive the signal from the membrane to the cell nucleus. There, the signal will result in the start-up of some genes, initially also turned off, which will turn on when receiving the signal. Activation of these genes is necessary for cell reproduction.
The protein KRAS it is turned off because it is attached to the molecule GDP. When a receptor that spans the membrane receives the growth factor signal, the part of the receptor inside the cell interacts with the protein. KRAS. It can now drop the GDP which leads united and unite instead GTP. This exchange of GDP by GTP turn on protein KRASactivates it, and now allows it to interact with other cellular proteins and in turn transmit the signal to them.
This transmission occurs only for a while, because, and here comes the wonderful thing about this mechanism, the protein itself KRAS turns off by itself This is achieved because the protein KRAS acts as an enzyme that converts GTP in GDPthat is, it removes a phosphate group from the GTP to leave it with two phosphate groups alone. Joined back to GDP the protein KRAS turns off.
We can now understand the effect of mutations in the gene that produces the protein KRAS that affect their enzymatic activity. If, due to a mutation, the protein KRAS once attached to GTP can’t turn it into GDP it will remain on forever, and will continuously communicate the received signal, even though it has already disappeared from the external environment. This signal of continued growth can cause cancer, as we have said. In fact, mutations in KRAS They are responsible for up to 20% of all cancers.
The results of the experiments of Dr. Varmus’s group indicated that, if we could somehow turn off the protein KRAS mutant, in the case of tumors that possess it, these could be cured. During the last two decades, research has been carried out to develop drugs capable of achieving this objective. Attempts are also being made to develop strategies based on destruction of the ARN messenger of KRAS mutant, and from that only, and in the generation of killer T lymphocytes capable of killing only the cells that possess the mutation, but not normal cells. Some of these studies are already in the clinical trial phase, although these have unfortunately only started very recently. Let us hope that they will succeed and that the basic research carried out twenty years ago and beyond will eventually be transformed into an effective anti-tumor tool.
(Jorge Laborda 10/11/2021)
Works by Jorge Laborda.
Your defenses against coronavirus
Your defenses against coronavirus
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Deflamed immunology: An introduction to the immune system and its pathologies
Kilo of Science Volume XII eBook
Kilo of Science Volume XII Paper
Kilo of Science Volume I. Jorge Laborda
Kilo of Science Volume II. Jorge Laborda
Kilo of Science Volume III. Jorge Laborda
Kilo of Science Volume IV. Jorge Laborda
Kilo of Science Volume V. Jorge Laborda
Kilo of Science Volume VI. Jorge Laborda
Kilo of Science Volume VII. Jorge Laborda
Kilo of Science Volume VIII. Jorge Laborda
Kilo of Science Volume IX. Jorge Laborda
Kilo of Science Volume X. Jorge Laborda
Kilo of Science Volume XI. Jorge Laborda
Matrix of homeopathy
Chained circumstances. Ed.Lulu
Chained circumstances. Amazon
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One moon, one civilization. Why the Moon tells us that we are alone in the Universe
One Moon one civilization why the Moon tells us we are alone in the universe
The thousand and one bases of ADN and other science stories
Adenius Fidelius
The intelligence funnel and other essays
The gods have been cloned
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