Researchers from Rockefeller University discovered oxygen sparse area in tumor cells that could be the target for new drugs against cancer.
A tumor simply grows to create more cancer cells. However, the process often leads to scarcity of oxygen supply that could suffocate the tumor cells. The oxygen scarcity could restrict production of aspartate required in many cellular processes. The research from The Rockefeller University led by Kivanç Birsoy, head of the Laboratory of Metabolic Regulation and Genetics is exploring the scenario to starve the tumor cells with new target drugs. Previous studies revealed that outgrowing blood supply in certain tumors leads to their slow growth in low-oxygen conditions. However, the exact reason behind the mechanism was not known as oxygen molecules are responsible for vast number of chemical reactions in the cell.
To identify the most responsible reaction, the team replicated the oxygen deprivation in tumor cells in the lab. While most of the cells grew surprisingly under low- oxygen levels, others exhibited low sensitivity and some remained undisturbed at all by the experiment. It was observed that most sensitive cells lost the amino acid aspartate under oxygen deprivation. Although cells unable to produce aspartate without oxygen, the resistant cells seem to derive it from their environment. A lack of aspartate in sensitive cells affects production of new proteins and synthesis of genetic material. The oxygen deprivation in the tumor cells led to the activation of a gene called SLC1A3 to suck up aspartate from their surroundings. Similar results were observed in the lab grown tumor cells, where SLC1A3 caused normally sensitive low oxygen- cells to grow faster. The results were same for tumors transplanted to mice, which further proved that aspartate can be a major factor for limiting tumor growth in low oxygen conditions. The research published in the journal Nature Cell Biology on June 27, 2018 could lead to development of new drugs to curb the growth of cancer cells by making them desperate for a supply of aspartate.