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What Goes Wrong with Normal Cells Which Lead To Cancer?

Story Highlights
  • Cancer is abnormal growth of cells which leads to tumor formation.
  • The angiogenesis process ensures supply of blood flow and nutrients to the growing cancer cell.
  • Improper regulation of cell cycle is a stepping stone to cancer.

Introduction: Cancer is a genetic disease caused by alteration within specific genes. These alterations can be acquired during the lifespan of an individual or be inherited from one or both parents. The Cancer cells ignore inhibitory signals and continue to grow in absence of stimulatory growth signals that are required for normal cells.  This leads to uncontrolled growth of abnormal cells. The cancer cells have certain markers which help us to distinguish them from normal cells. We can see the differences in normal cells and cancerous cells in the picture below [1].

Fig 1. A comparison between structural variation of normal and cancer cells [6].
Types of tumors and Angiogenesis :

Tumors are of two types:  Benign and malignant.

Benign are the ones that do not spread or invade other parts of the body and hence are less dangerous. Malignant tumors have the capability to invade different parts of the body. In cancer, the normal healthy cells are replaced by cancerous cells. Cancer cells require comparatively much more nutrients, oxygen and blood supply to that of normal cells. To meet their requirements the cancer cells form blood vessels of their own by the process of angiogenesis. These blood vessels along with supporting the growth also helps in removing their waste products. They also provide the conduits for cancer cells to spread to other sites of the body.  Cancer cells promote angiogenesis by secreting growth factors like VEGF that act on endothelial cells stimulating them to proliferate and develop into new blood vessels.  Just as there are stimulants of angiogenesis, there are also inhibitors. Naturally occurring inhibitors are endostatin and thrombospondin. Synthetic inhibitors include antibodies and synthetic compounds directed against integrins, growth factors and growth receptors. Preclinical trials on mice and rats suggest angiogenic inhibitors might be effective in stopping tumor growth [5].

Cell cycle and it`s relation to cancer :

The cell cycle has 4 major stages of cell cycle: G1, S, G2 and M. There are 4 checkpoints where the DNA replication is regulated and if they encounter any damage or miss replicated DNA the cell cycle is arrested. It stops, repairs the damage and only then it moves on. The first checkpoint is the G1 checkpoint where the DNA damage is corrected prior to the cell entering the S-phase. The second is the S checkpoint where continuous monitoring of the integrity of DNA takes place. This checkpoint could also be called the quality control checkpoint of DNA synthesis. The next is the G2 checkpoint which prevents initiation of mitosis until entire DNA is replicated. Damage to the DNA caused by irradiation is also detected and repaired here. The last checkpoint is M checkpoint where chromosomal spinal attachments are checked [3].

Fig 2. Cell cycle regulation and it’s checkpoints [3].

Failure in any checkpoint could lead to replication of wrongly synthesized DNA which would in turn lead to incorrect decoding of the message from the DNA, disruption in the cellular processes, abnormal cell behaviour and finally cancer.

Failure of p53 gene :

Another major cause of cancer is failure in p53 regulation. P53 gene is considered to the “guardian of the genome” as it has a major role in protection of the cell acting as an antitumor weapon. When a cell is under stressful conditions e.g. DNA damage, there is accumulation of p53 in the nucleus of the cell. This leads to pro-apoptotic function. The p53, once activated promotes the arrest of cell cycle and promotes either DNA repair and/or apoptosis. This prevents the propagation of cells with damaged DNA. Thus, the DNA-binding activity of p53 is tightly linked to its tumor suppressive function [6]. The failure in p53 regulation could lead to Li-Fraumeni syndrome. Victims of this disease are afflicted with a very high incidence of cancer and leukaemia. The main cause of these mutations is exposure to mutagens through atmosphere, diet, exposure to radiation etc. The only preventive major is to avoid the carcinogens [7].

Conclusion :

The cause of cancer is genetic mutations. The malignant tumor metastasizes invading other tissues. The tumor gets nutrients from angiogenesis. Failure in cell cycle regulation and p53 gene is a major cause of cancer.

COPYRIGHT: This article is the property of We Speak Science, a non-profit establishment co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by Nipurna Murkar, K.J. Somaiya College, Mumbai, India

References:

  1. National cancer Institute- Understanding cancer.
    https://www.cancer.gov/about-cancer/understanding/what-is-cancer
  2. Cell Cycle Regulation by Checkpoints, Kevin J. Barnum and Matthew J. O’Connell PMCID: PMC4990352, NIHMSID: NIHMS734418
  3. Cell Cycle Checkpoint and DNA Damage Response Defects as Anticancer Targets: From Molecular Mechanisms to Therapeutic Opportunities Loredana Spoerr et. al
  4. Cancer Cells vs. Normal Cells: How Are They Different? By Lynne Eldridge, MD
  5. Skull with Cigarette by Vincent Van Gogh
  6. Cancer Cells vs. Normal Cells: How Are They Different? By Lynne Eldridge, MD
  7. Role of p53 in Cell Death and Human Cancers Toshinori Ozaki and Akira Nakagawara

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