Signaling Defects & Cancer: Study with Video Lessons, Practice Problems & Examples

Defects in biosignaling pathways can lead to diseases like cancer, characterized by uncontrolled cell growth. Two key gene types regulate this process: proto-oncogenes, which promote normal cell division (acting like a green light), and tumor suppressor genes, which inhibit cell division (acting like a red light). Mutations can convert proto-oncogenes into oncogenes, promoting cancer, while mutated tumor suppressor genes fail to inhibit growth, akin to broken brakes. Understanding these mechanisms is crucial for grasping cancer development and potential therapeutic targets.

Signaling Defects & Cancer

So now that we've covered all of the biosignaling pathways that we're going to cover in our clutch prep biochemistry course, we're going to move on and talk about signaling defects and cancer. Thus, defects in biosignaling pathways can cause the biosignaling pathways to fail to elicit the cell response, and that will lead to disease. Cancer is a very specific type of disease characterized by uncontrollable and inappropriate cell growth, and it is also associated with signaling defects. In our next lesson video, we're going to introduce the types of genes that control cell growth so that we can take a better look at understanding how cancer can develop. I'll see you guys in our next video.

Signaling Defects & Cancer

So in this video, we're going to introduce the 2 types of genes that regulate cell growth. And again, in a healthy and normal cell, there are 2 types of genes that regulate cell growth that we have numbered down below, number 1 and number 2, and so the first one is going to be proto-oncogenes. Now proto-oncogenes are genes themselves that provide signals that promote appropriate cell division. And so, proto-oncogenes pretty much act like the green light for cell division, allowing cell division to proceed again at a normal and healthy appropriate rate. And so if we take a look at our image down below at the proto-oncogene, notice that we're pretty much saying here that it acts like the green light for cell division, allowing cell division to proceed at a normal and healthy rate at an appropriate rate. And so proto-oncogenes are pretty much acting like the gas pedal for cell division. And so a classic example of a proto-oncogene is the gene that encodes the monomeric G protein Ras, which recall Ras was found in the insulin RTK signaling pathway as a growth hormone. And so when the Ras G Protein is active, it will appropriately and healthily and normally stimulate or promote cell growth. And so Ras is a classic example of a proto-oncogene.

Now the second type of gene that is again found in healthy and normal cells that regulate cell growth, are these tumor suppressor genes. And so the tumor suppressor genes, as their name is going to be genes that provide signals that suppress or inhibit cell division. And so tumor suppressor genes pretty much act like the red light for cell division, inhibiting cell division, acting like the brakes for cell division. And so if we take a look at our image down below, notice that we're showing you that tumor suppressors pretty much act like the red light for cell division to again stop or inhibit cell division from proceeding and so, pretty much tumor suppressors act like the brakes to cell division, inhibiting cell division, again at a healthy and normal rate of inhibition. And so a classic example of tumor suppressor genes are the genes that encode the phosphate groups, and so they reverse the kinase activity. And so phosphatases, which we have seen are involved with the termination or the inhibition of a signal, would be used to inhibit the signal and inhibit cell growth, again as we just indicated here.

And so this is the end of our introduction to the types of genes regulating cell growth. And again, in healthy and normal cells, there are proto-oncogenes, which act as the green light for cell division, and tumor suppressor genes which act as the red light for cell division. And so this here concludes this video, and I'll see you guys in our next one.

Signaling Defects & Cancer

In this video, we're going to introduce how oncogenes, which are different than the proto oncogenes that we introduced in our last lesson video, and mutated tumor suppressor genes actually promote cancer. Although the proto oncogenes that we talked about in our last lesson video are healthy, normal, and essential, they are also really susceptible to mutations that generate oncogenes. Oncogenes are different than proto oncogenes. Proto oncogenes are normal, healthy, and essential, whereas oncogenes are bad because they are mutated genes that promote unrestrained cell growth or essentially oncogenes are mutated genes that promote cancer. These are bad genes that we do not want. The proto oncogene encoding the monomeric G protein called Ras is actually one of the most commonly mutated in human cancer tumors. When the proto oncogene encoding Ras is mutated, it becomes an oncogene. Notice down below, on the left-hand side in image number 1, we're showing you how oncogenes can lead to cancer development, and on the right-hand side in image number 2, how mutated tumor suppressor genes can lead to cancer development. We'll start off with image number 1 here. Of course, the number 1 in the text corresponds with the number 1 in the image. What we're showing you is that the most common mutation in cancer tumors is the loss of Ras's intrinsic GTPase activity. Recall from our previous lesson videos when we covered insulin RTK biosignalling, that the GTPase activity of a G protein will cleave the high energy active GTP into the low energy inactive GDP. The GTPase activity is used to inactivate the G protein. However, if there is a mutation that leads to the loss of the GTPase activity, then the G protein will not be able to inactivate itself. That means it's going to keep Ras in the active state. If Ras is in the active state, it's going to overstimulate or overpromote cell growth leading to unrestrained cell growth and cancer. In our image number 1 below, notice that at the top we're showing you our ligand binding to the receptor, leading to a series of signal transduction events that ultimately makes its way into the nucleus to affect transcription factors that affect the transcription of particular genes in our DNA. Notice here we're showing you an oncogene, and it's an oncogene, which means that it has a mutation in it. When the transcription factors promote the transcription of this oncogene here, it's going to lead to the mutated Ras protein. This mutated Ras protein is going to have a loss of intrinsic GTPase activity, which means it will not be able to inactivate itself and will therefore remain in the active state. We know mutated Ras is going to overstimulate cell growth and lead to the development of cancer. In image number 2, we show you how mutations in tumor suppressor genes such as phosphatases can also lead to cancer development. In our image below in image number 2, notice again that we're showing you the ligand binding to the receptor here in the membrane, leading to a series of signal transduction events that make its way into the nucleus to activate specific transcription factors. Notice here that the DNA gene we're showing you is for a mutated tumor suppressor gene. Normally, we know that tumor suppressor genes are healthy, normal, and essential, and they are used as brakes to help inhibit cell growth. However, if you have a mutated tumor suppressor gene, that means you have broken brakes. When these transcription factors promote the transcription of the mutated tumor suppressor gene, it's going to lead to a mutated phosphatase—this yellow protein that we're showing you here. The mutated phosphatase will not be able to work or function properly, meaning it will not be able to remove phosphate groups and reverse the activity of phosphatases. It will be unable to inhibit cell growth, and therefore, it's going to promote cancer. It's almost like having broken brakes. If you have broken brakes that will not stop cell growth, then cell growth is going to be promoted, and cancer will be promoted. This concludes our lesson on how oncogenes and mutated tumor suppressor genes promote cancer. As we move forward in our course, we'll be able to get some practice applying these concepts. I'll see you guys in our next video.

Is there a difference between oncogenes and tumor suppressor genes?

• A. Yes, oncogenes are genes that can cause cancer when they become mutated to become proto-oncogenes, whereas tumor suppressor genes play no role in cancer.
• B. Yes, oncogenes prevent cancer from forming unless they are mutated to become proto-oncogenes, whereas tumor suppressor genes stimulate the formation of cancer even in the absence of mutation.
• C. No, oncogenes and tumor suppressor genes both stimulate the development of cancer, even in the absence of their becoming mutated.
• D. Yes, oncogenes are mutated versions of genes that promote abnormal cell division (such as mutated Ras), whereas tumor suppressor genes are genes that normally inhibit cell division.
• E. No, since both types of genes contribute to the development of cancer, there is no difference between them.

The protein product of the Ras oncogene is a mutated Ras protein. All of the following would be true EXCEPT:

• A. The Ras protein is a G-protein and functions as an internal clock.
• B. G-proteins have evolved to stay active for a certain length of time.
• C. Ras protein is active in cell growth and division.
• D. Ras can mutate so that it is less active as a GTPase.
• E. A less active GTPase would mean less stimulation of the MAP kinase pathway.

How does a proto-oncogene differ from an oncogene?

• A. Proto-oncogenes code for proteins that regulate expression of structural genes; oncogenes code for nucleic acids involved in cell division.
• B. Proto-oncogenes control normal cell division; oncogenes contribute to the development of cancer.
• C. When oncogenes become damaged, they become proto-oncogenes.
• D. Oncogenes activate tumor suppressor genes; proto-oncogenes repress tumor suppressor genes.
• E. Proto-oncogenes cause cells to self-destruct when damaged; oncogenes cause damaged cells to repair themselves.

Here’s what students ask on this topic:

What are proto-oncogenes and how do they function in normal cell growth?

Proto-oncogenes are genes that play a crucial role in normal cell growth and division. They act like a green light, promoting cell division at a healthy and controlled rate. Essentially, they function as the gas pedal for cell division. A classic example of a proto-oncogene is the gene encoding the monomeric G protein Ras, which is involved in the insulin RTK signaling pathway. When Ras is active, it stimulates cell growth appropriately. However, when proto-oncogenes mutate, they can become oncogenes, leading to uncontrolled cell growth and cancer.

How do tumor suppressor genes prevent cancer?

Tumor suppressor genes act as the brakes for cell division, inhibiting cell growth and preventing uncontrolled cell proliferation. They provide signals that suppress or inhibit cell division, ensuring that cells do not divide uncontrollably. A classic example of a tumor suppressor gene is the gene encoding phosphatases, which reverse kinase activity and terminate signaling pathways. When these genes are mutated, they fail to inhibit cell growth, leading to unrestrained cell division and potentially cancer. Essentially, mutated tumor suppressor genes are like broken brakes, unable to stop cell growth.

What is the difference between proto-oncogenes and oncogenes?

Proto-oncogenes are normal, healthy genes that promote cell division and growth at a controlled rate. They act like a green light for cell division. Oncogenes, on the other hand, are mutated versions of proto-oncogenes. These mutations cause the genes to promote unrestrained cell growth, leading to cancer. For example, the proto-oncogene encoding the Ras protein can mutate into an oncogene, resulting in the loss of its intrinsic GTPase activity. This keeps Ras in an active state, overstimulating cell growth and contributing to cancer development.

How do mutations in tumor suppressor genes lead to cancer?

Mutations in tumor suppressor genes lead to cancer by disabling the genes' ability to inhibit cell growth. Normally, tumor suppressor genes act as brakes, preventing uncontrolled cell division. When these genes are mutated, they lose their function, akin to having broken brakes. For instance, a mutated tumor suppressor gene encoding a phosphatase will fail to remove phosphate groups and reverse kinase activity, leading to unrestrained cell growth. This inability to inhibit cell division promotes cancer development, as the cells continue to proliferate uncontrollably.

What role does the Ras protein play in cancer development?

The Ras protein, encoded by a proto-oncogene, plays a significant role in cell growth and division. In its normal state, Ras promotes healthy cell growth by activating signaling pathways. However, when the proto-oncogene encoding Ras mutates, it becomes an oncogene. This mutation often results in the loss of Ras's intrinsic GTPase activity, preventing it from inactivating itself. Consequently, Ras remains in an active state, continuously stimulating cell growth. This unrestrained cell growth leads to the development of cancer, making Ras one of the most commonly mutated genes in human cancer tumors.