Cell Cycle Control and Cancer Implications

Hey all!

This blog post is a part of STEM Talks’ ever expanding General Biology Series. For this post, it is recommended you understand the basics of cell division and cell cycle phases.

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The cell cycle seems to be governed by cytoplasmic and extracellular signals. A cell cycle control system controls the cell cycle. It is a cyclically operating set of molecules that can trigger and coordinate different events and passages through checkpoints (explained later). The timing, frequencies, and rate of cell division is crucial and varies by cell type.

Checkpoints are parts of the cell cycle where stop or go signals can help or inhibit the cell from passing into the next stage of its life. There are three major checkpoints – G1, G2, and M corresponding to their respective cell cycle phases. The G1 Checkpoint needs to be passed for a cell to go into its initial growth phase of the cell cycle. If there is no go ahead signal a cell will go into a state called the G0 phase where it cannot divide. Many cells in the body such as Nerve and Muscle cells are in G0 stage for the lifespan of the organism. Some cells like Liver Cells are in G0 but if damaged can divide once but then go back to G0.

In Mitosis, the Kinetochore of the chromosome attaches to the ever expanding mitotic spindle microtubule. If a chromosome is not attached to the kinetochore, the cell cannot continue with mitosis (M Checkpoint). This is so that the daughter cells do not have an abnormal amount of chromosomes. If all chromosomes are attached, a metabolic pathway occurs where an enzyme called Separase cleaves the Cohesins causing the sister chromatids to stick together.

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To understand the G2 checkpoint, more needs to be known about the cell cycle control mechanism. The number of mechanism molecules determines the pace of cell activities. For the G2 phase there are two main molecules. Protein Kinases are enzymes that activate or inactivate other proteins through ATP Phosphorylation. To be active, protein kinases must be chemically bonded to another molecule called Cyclins. These molecules are names after their fluctuating concentrations in the cell. When Protein Kinases bond to Cyclins, the resultant complex is called a Cyclin Dependent Kinase (CDK).

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Maturation Promotion Factor (MPF) is a CDK that causes cells to pass into M phase once the G2 checkpoint is passed. In addition, it activates other Protein Kinases that play minor roles in regulation. In addition to helping the cell pass through the G2 Checkpoint, MPFs contributes to the condensation of chromatin fibers into chromosomes in the first stage of mitosis, Prophase.

In Anaphase, MPFs switches itself off and the cyclin breaks off and is destroyed. The remaining CDK will stay behind for the next cycle.

Many physical and chemical factors from outside the cell can also effect cell division by inhibiting it. For example, cells cannot divide if it lacks a specific molecule needed for development or growth. Growth Factors are released by certain cells that stimulate the cell division of other cells. From the standpoint of the other cells, the growth factors are extracellular signals. An example of a growth factor in the human body would be Platelet Derived Growth Factors (PDGF). PDGFs are needed for connective tissue cells called Fibroblast to divide. This happens when the PDGF binds to its specialized receptor on a cell membrane. This results in a signal transduction pathway takin g place that allows the Fibroblast to pass the G1 checkpoint.

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Growth Factors are chemical, now we will look into physical factors. Density Dependent Inhibition is when crowded cells stop their cell division process. When specific receptors on two similar cells meet, both cells send inhibition signals stopping cell division. In addition to this, cell sneed to be attached to something to divide. This is called Anchorage Dependence.

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Cancer does not listen to any cell cycle control. This is what makes Cancer one of the most deadly disease complexes. For example, cancer cells do not heed neither density dependent inhibition nor anchorage dependence. Cancer Cells also do not heed growth factors from other cells. Sometimes, cancer can stop dividing but it does so completely randomly and not at the designated cell cycle checkpoints. Many cancers make the growth factors within their own cells while others alter their own metabolic pathways such that they don’t need growth factors at all. Cancers come from abnormalities in genes as genes encode all of life.

Cancer cells can divide forever if given proper nutrition. For example, cancer cells from a woman named Henrietta Lacks, who died in 1951, are still alive!

The process of a normal cell become cancerous is called transformation. Usually the transformed cells have different recognition receptors on the cell membrane and the immune system designates it as an invader and promptly destroys it. If they do not, the cells can form a tumor. Benign tumors do not cause too many problems and can be treated with pills or an invasive procedure such as a surgery. Malignant Tumors can metastasize and spread to other areas of the body.

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There are two main therapies for metastasis. One is high doses of lethal radiation that is aimed at the cancer. This causes abnormalities and kills the cells. Another method is called chemotherapy where toxic drugs and chemicals are administered. Chemotherapy is somewhat effective (very good outcome for cancer diseases) but as a side effect harm cells that divide rapidly by nature. An example chemotherapeutic drug called Taxol stops the mitotic spindle from forming but it also affects other nearby cells.

Unfortunately, death rates for cancer are extremely high but are improving each year due to the tens of millions being poured into research and pharmaceuticals.

To see how gene editing techniques are used in treating cancer and how they can change genomes, check out our genomics series!

See ya for now!

-SAI RACHAKONDA

 

 

 

 

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