The Hallmarks of Cancer: 9 - Reprogramming Energy Metabolism
The 9th article in my series is finally published! To coincide with this, I also want to announce my (newish) website - Jargonwall (http://www.jargonwall.com/). For now, it is an archive of all my science articles, easily searchable and under my own control. It feels really good to have my own website, and have my own ‘home’ for my outreach efforts. I will continue posting about science here on G+, but I will also use Jargonwall for longer articles explaining detailed molecular biology processes minus the jargon. I don’t have any ads on my site, and I’ve also made sure that it displays well on mobiles and tablets. I hope you enjoy it!
The Hallmarks of Cancer are ten anti-cancer defense mechanisms that are hardwired into our cells, that must be breached by a cell on the path towards cancer. The Ninth Hallmark of Cancer is defined as “Reprogramming Energy Metabolism”. You can read the detailed article here (http://goo.gl/Au7vQD), and the previous Hallmarks of Cancer articles can be found here (http://goo.gl/6F1Q7q).
✤ Uncontrolled growth defines cancer. Growth requires a cancer’s cells to replicate all of their cellular components; their DNA, RNA, proteins and lipids must all be doubled in order to divide into daughter cells. Of course, this process requires energy. Cancer cells must adjust their metabolism accordingly, to enable this frenzied growth.
✤ Cancer cells switch their metabolic pathway, from normal respiration to a process known as aerobic glycolysis. Cancer cells consume more than 20 times as much glucose compared to normal cells, but do so through an inefficient metabolic pathway. Why do cancer cells do this, when they can obtain sixteen times as much ATP per molecule of glucose by opting for normal respiration?
✤ Although cancer cells produce far less ATP per molecule of glucose, they produce it much faster. Cancer cells produce ATP almost a hundred times faster than normal cells. It is essentially a cost-benefit calculation, where the benefits of speedy ATP production outweigh the costs associated with inefficient glucose breakdown. Cancer cells undergoing aerobic glycolysis also produce many intermediate biosynthetic precursors. These molecules are used as building blocks for the production of proteins, lipids and DNA required by the rapidly dividing cells.
✤ Cancer cells are addicted to these metabolic precursors; the enzymes that control these pathways are often over-expressed or mutated in cancer cells. This addiction is exploited in chemotherapy strategies. For example, 5-fluorouracil, methotrexate, and pemetrexed inhibit the biosynthesis of DNA precursor molecules. The high glucose consumption of cancer cells is also exploited when imaging cancer; Positron Emission Tomography (PET) combined with Computer Tomography (PET/CT) is used to detect the absorption of the glucose analogue fluorodeoxyglucose (FDG) by tumours, and has a better than 90% sensitivity and specificity for the detection of metastases of most cancers.
✤ Cancer cells do not function in isolation. Tumours are complex tissues, made up not only of cancer cells, but blood vessels, immune cells and other bystanders. These healthy cells are co-opted and subverted to perform tasks that support cancer progression. The cellular pathways described in the Hallmarks of Cancer are not only interconnected, the body’s own cells, when trapped inside the tumour microenvironment, engage in complementary metabolic pathways, supporting and encouraging cancer cell survival and growth.
Image adapted from Jens Maus, Wikimedia Public Domain (http://goo.gl/jXjR9P)