If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences.
The research team analyzed samples of messenger RNA data—also called transcriptomic data—from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published in the early online edition of the Journal of Molecular Cell Biology.
Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells.
"Cancer drugs try to get to the root—at the molecular level—of a particular mutation, but the cancer often bypasses it," Xu said. "So we think that possibly genetic mutations may not be the main driver of cancer."
Much of cancer research so far has focused on designing drug treatments that counteract genetic mutations associated with a particular type of cancer. In their study, the researchers analyzed data downloaded from the Stanford Microarray Database via a software program to detect abnormal gene expression patterns in seven cancers: breast, kidney, liver, lung, ovary, pancreatic and stomach. The online database allows scientists to examine information from microarray chips, which are small glass slides containing large amounts of gene material.
Xu relied on the gene HIF1A as a biomarker of the amount of molecular oxygen in a cell. All seven cancers showed increasing amounts of HIF1A, indicating decreasing oxygen levels in the cancer cells.
Low oxygen levels in a cell interrupt the activity of oxidative phosphorylation, a term for the highly efficient way that cells normally use to convert food to energy. As oxygen decreases, the cells switch to glycolysis to produce their energy units, called ATP. Glycolysis is a drastically less efficient way to obtain energy, and so the cancer cells must work even harder to obtain even more food, specifically glucose, to survive. When oxygen levels dip dangerously low, angiogenesis, or the process of creating new blood vessels, begins. The new blood vessels provide fresh oxygen, thus improving oxygen levels in the cell and tumor and slowing the cancer growth—but only temporarily.
"When a cancer cell gets more food, it grows; this makes the tumor biomass bigger and even more hypoxic. In turn, the energy-conversion efficiency goes further down, making the cells even more hungry and triggering the cells to get more food from blood circulation, creating a vicious cycle. This could be a key driver of cancer," Xu said.
Xu explained that this new cancer-growth model could help explain why many cancers become drug resistant so quickly—often within three to six months. He stressed the importance of testing the new model through future experimental cancer research. If the model holds, researchers will need to search for methods to prevent hypoxia in cells in the first place, which could result in a sea change in cancer treatment.
Additional authors of this study include Juan Cui, Xizeng Mao and Victor Olman, all of UGA, and Phil Hastings of Baylor College of Medicine. Xu also has a joint appointment with Jilin University in China.
Ying Xu | EurekAlert!
Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University
Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Earth Sciences
27.03.2017 | Life Sciences
27.03.2017 | Life Sciences