The Outcomes
The Hallmarks of Cancer
Gene Mutations
Oncogenes
Proto-oncogenes are genes that normally help cells grow. When a proto-oncogene mutates (changes) or there are too many copies of it, it becomes a "bad" gene that can become permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer. This "bad" over reactive cancer-promoting gene is called an oncogene.
The Cell Cycle
To divide, a cell must grow, copy its genetic material (DNA), and physically split into two daughter cells. In eukaryotic cells, the phases of the cell cycle are divided into two major phases: interphase and the mitosis (M) phase.
During interphase, the cell grows and makes a copy of its DNA.
Preparation for division happens in three phases:
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G1 : the cell grows physically larger, copies organelles, and makes the molecular building blocks it will need in later steps.
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S : the cell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome. The centrosomes help separate DNA during M phase.
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G2 : the cell grows more, makes proteins and organelles, and begins to reorganize its contents in preparation for mitosis. G_22start subscript, 2, end subscript phase ends when mitosis begins.
During the mitosis (M) phase, the cell separates its DNA into two sets and divides its cytoplasm, forming two new cells.
Involves: Mitosis and Cytokinesis
In mitosis, the nuclear DNA of the cell condenses into visible chromosomes and is pulled apart by the mitotic spindle, a specialized structure made out of microtubules. Mitosis takes place in stages: prophase, prometaphase, metaphase, anaphase, and telophase. For cytokinesis, the cytoplasm of the cell is split in two, making two new daughter cells.
Regulation
Cell cycle regulation is controlled by checkpoints and special regulatory proteins. These special proteins are called cyclin-dependent protein kinases, Cdks. These kinases transfer phosphate groups to proteins that initiate or regulate important cell cycle events such as DNA replication, and this transfer event modifies the activity of these proteins. The activities of Cdks vary with regard to different stages of the cell cycle, and their activity is dependent on another group of proteins called cyclins. Cyclins, are present only at certain times during the cell cycle. There are different types of cyclins for the different phases of the cell cycle, and their appearance in the cell varies because they are targeted for destruction when they are no longer needed.
Dysfunction
If the cell cycle regulation proteins were defective then even faulty cells would be able to pass through the checkpoints. Thus mutated regulatory proteins would allow the faulty cells to continue to grow and divide, promoting the abnormal proliferation rate of the faulty cells that could potentially lead to a tumor growth that would ultimately lead to cancer.
Tumor Suppressor Genes
A tumor suppressor gene, or anti-oncogene, are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die. When this gene mutates to cause a loss or reduction in its function, thus progressing the cell to cancer, usually in combination with other genetic changes. A tumor suppressor gene is like the brake pedal on a car. It normally keeps the cell from dividing too quickly, just as a brake keeps a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can get out of control.
External / Internal stimuli Lead to Apoptosis
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, 35(4), 495–516. http://doi.org/10.1080/01926230701320337
In a normal healthy cell the outer membrane of the mitochondria displays a protein called as Bcl-2. Any internal damage (examples damaged DNA, chromosome rearrangement, hang ups in division, hypoxia, etc.) to the cell will cause inhibition of this protein that will lead to the activation of Bax protein encoded by a family of pro-apoptotic genes. Thus the process of apoptosis will be activated. It is like the cell is saying "I'm too damaged, I must die".
Extrinsic or death receptor pathway is mediated by Fas and TNF receptors present on the cell membrane of target cell. Any external stimulus in the form of ligand binds to them, thus activating them and initiating a cascade of caspase cleavages leading to apoptosis. This is like the cell is saying "I'm too mutated, or dangerous, or infected so I must die".
In essence, both pathways activates the caspase cascade at some point that results in apoptosis; either way the actual process of apoptosis is carried out by the cell itself in a programmed, regulated manner.
The Escape from Death
Evasion of apoptosis can be acquired by the cells using a variety of strategies:
[1] The P53 gene, dubbed as the guardian of the genome, is one of the most commonly mutated tumor suppressor gene. The resultant inactivation of the p53 protein is responsible for giving half of the tumors apoptosis evasive characteristics.
[2] Another pathway involved is the P13 Kinase-AKT/ PKB pathway, which is concerned with the anti-apoptotic survival signals. This survival signaling circuit is found to be upregulated either by extracellular factors such as IGF-1 and IL-3, or by intracellular signals involving RAS, thus leading to evasion of apoptosis.
[3] Many calls employ the activation of the transcription factor NF-κB, which may be caused by TNF activation. Such cells are resistant to stimuli that can induce apoptosis. Inhibition of NF-κB nuclear translocation enhances cell death by apoptosis in these cells.
In conclusion, the evasion of apoptosis when combined with telomerase activation, which gives the cells unlimited proliferative potential, leads to the expression of a highly malignant phenotype.
Metastasis
Cancer cells spread through the body in a series of steps. These steps include:
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Growing into, or invading, nearby normal tissue
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Moving through the walls of nearby lymph nodes or blood vessels
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Traveling through the lymphatic system and bloodstream to other parts of the body
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Stopping in small blood vessels at a distant location, invading the blood vessel walls, and moving into the surrounding tissue
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Growing in this tissue until a tiny tumor forms
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Causing new blood vessels to grow, which creates a blood supply that allows the tumor to continue growing
Inflammation Leads to Cancer
Inflammation is a normal physiological response that causes injured tissues to heal. The inflammatory process starts when the damaged tissue sends a signal for chemicals to be released. In response, white blood cells make substances that cause cells to divide and grow to rebuild tissue to help repair the injury. Once the wound is healed, the inflammatory process ends.
In chronic inflammation, the inflammatory process could begin even if there is no injury, and it does not end when it is supposed to. Chronic inflammation is usually caused by infections that don’t go away, abnormal immune reactions to normal tissues, or conditions such as obesity. Over time, the chronic inflammation causes DNA damage because the substances that cause the cells to divide and grow does not stop properly and ultimately leads to cancer. For example, people with chronic inflammatory bowel diseases, such as Ulcerative colitis and Crohn disease, have an increased risk of colon cancer.
Role of the Diet
Your body needs vitamins and minerals to perform essential functions, grow and develop, and repair itself. Some vitamins, minerals, and other nutrients help protect your body against damage from oxidants.
Vitamins and Folate:
High vitamin D levels were previously thought to reduce cancer risk, and although recent evidence supports this association for some cancer sites, it also provides evidence of an increased risk of some rarer cancers, including pancreatic and esophageal cancer. Folate plays an essential role in DNA methylation and is necessary for the synthesis of thymine. Folate deficiency can lead to misincorporation of uracil instead of thymine into DNA and increases the number of chromosomal breaks. Previous prospective cohort studies have reported a suggested 20% to 40% reduced risk of colorectal cancer for individuals with the highest folate intake.
Fruits and vegetables, which are good sources of fiber, increase stool bulk, decrease transit time in the colon, and dilute potential carcinogens.
Plant-based Foods:
Fruits and vegetables protect against several cancers, including mouth, throat, voice box, esophagus, stomach, lung, pancreas, and prostate. It is likely that the various phytochemicals in fruits and vegetables work together to lower cancer risk. Some help regulate hormones, such as estrogen. Others slow cancer cell growth or block inflammation. Many lower the risk of damage caused by oxidants, such as tobacco or ozone.
