Introduction
Metastasis occurs when cancer cells break off from the original tumor, which is also called the primary tumor, travel through the body, and begin to grow in other tissues and organs. Metastasis causes death by damaging important organs such as the brain, lungs, and liver. Metastasis is the end result of a complex, multi-step biological process known as the metastatic cascade or the seed and soil hypothesis. The genetic basis of tumorigenesis (accumulation of malignant properties in the normal cells) may vary between tumor types, but the cellular and molecular steps necessary for metastasis are generally similar among solid tumors. Mutations can happen often. A mutation can be beneficial, harmful, or neutral. This depends on where the change will occur in the gene. A single mutation usually does not cause cancer. Cancer can occur from multiple mutations over a lifetime. This is why cancer occurs more often in old age people. Older people have had more opportunities for mutations to build up.
What Is the Molecular Basis of Metastasis?
Cancer cells tend to spread to certain places in the body depending on the site where the tumor first formed. For example, breast cancer tends to spread to the bones, lungs, liver, and brain, and colon cancer tends to spread to the lungs and liver. It is important to remember that a metastatic tumor is the same type of cancer as a primary tumor. For example, colon cancer cells have traveled through blood vessels and formed metastatic tumors in the liver. But these metastatic tumors are colon cancer and not liver cancer.
What Is the Role of Cancer Genes?
There are two types of genes that, when mutated, are involved in the development of cancer. These are tumor suppressor genes and oncogenes. Some tumor suppressor genes code for proteins that slow down or prevent unregulated cell growth. Others detect abnormalities in cells and can encourage cellular repair or promote cell death (apoptosis). Mutations can occur in these genes that lead to a non-functional protein being produced. If one copy of the gene is mutated, there is no direct effect on the cell because the other copy of the gene still codes for a working protein. However, if the second copy of the gene is also mutated, the tumor suppressor no longer codes for any working protein. This means the cell can divide without regulation because both copies must be mutated to cause cancerous growth.
Proto-oncogenes code for proteins involved in promoting cell growth and development. They are like the accelerator in the cell, driving the growth cycle forward. Oncogenes are mutated versions of proto-oncogenes. The mutation results in proteins that promote continuous cellular growth by remaining switched on. They continue to promote cell growth in the presence of signals that would normally halt the cell growth cycle. Unlike tumor suppressor genes, only one copy of the proto-oncogene is required to promote unregulated cell growth. Oncogenes are considered dominant cancer genes. If cell growth is no longer controlled, it will divide inappropriately, forming a tumor. The fast, poorly controlled division of these cells also allows more cancer-promoting changes in their DNA (deoxyribonucleic acid) to build up rapidly.
What Causes Genetic Changes?
Genetic changes which are responsible for causing cancer can be inherited, or they can arise from certain environmental exposures. Genetic changes can also arise because of errors that occur as the cells divide. The mutations or genetic changes are responsible for cancer; the following are the cause:
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Hereditary - Genetically, people get it from their genes, and they have more expression of oncogenes.
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Ultraviolet Radiation - High exposure to UV (ultraviolet) radiation can cause cancer.
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Chemicals - Certain chemical exposure increases the chances of getting cancer.
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Viruses - Hepatitis B, Hepatitis C, Ebstein-Barr, and human papillomavirus may cause cancer.
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Smoking - It is one of the major reasons for cancer. The smoke releases polyaromatic hydrocarbons, which are responsible for cancer.
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Cell Dividing - Genetic changes continue to divide cells which causes cancer.
What Are the Epigenetics of Cancer Metastasis?
Epigenetic changes include altered deoxyribonucleic acid (DNA) methylation and histone modification patterns that result in chromosomal instability, changes in chromatin compaction, and changes in gene expression. Several recent studies have discovered that epigenetic changes may play a significant role in metastasis. For example, an analysis of aggregated transcriptomic data from melanoma patient samples found that upregulated aldehyde dehydrogenase-1 (ALDH1A1) and heat shock protein (HSP90AB1), and downregulated receptor tyrosine kinase (KIT), keratin-16 (KRT16), small proline-rich protein-3 (SPRR3), and transmembrane protein (TMEM45B) distinguished metastatic melanomas from their primary counterparts despite the absence of mutation or copy number alterations (CNA) in these loci; notably, several immunohistochemical studies have correlated reduced KIT expression with metastatic potential.
Another study found that metastatic melanomas contain a reduced expression of Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (LFNG), which encodes an enzyme that glycosylated neurogenic locus notch homolog protein (NOTCH) and thereby increases its signaling, and demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) knockdown of LFNG leads to increased pulmonary metastases in a mouse model. Other epigenetic changes associated with melanoma metastasis include loss of 5-hydroxymethylcytosine (5-hmC) bases in DNA likely due to downregulation of isocitrate dehydrogenase (IDH2) and ten-eleven translocation (TET) family enzymes, reduced expression of the non-metastatic protein (NM23), overexpression of ras homolog family member C (RhoC), and downregulation and nuclear localization of breast cancer metastasis suppressor-1 (BRMS1). In addition to melanoma, DNA hypermethylation within tumor suppressor gene promoters, including breast cancer gene-1 (BRCA1), has been associated with metastatic progression in breast, lung, colorectal, and liver cancer.
What Are the Challenges in Understanding Cancer Genetics?
According to researchers, not every cancer is linked to a specific gene. Cancer usually involves multiple gene mutations, and some evidence suggests that genes also interact with their environment, which further complicates understanding the role of genes in cancer.
Conclusion
Genes control how the cells work by making proteins. These proteins have specific functions, and they act as messengers for the cell. Each gene should have the correct instructions for making its protein which allows the protein to perform the correct function for the cell. All types of cancer begin when one or more genes in a cell mutate. A mutation is a change; it creates an abnormal protein or may prevent a protein’s formation. An abnormal protein will provide different information than a normal protein which can cause the cells to multiply uncontrollably and become cancerous.
