The "life gate" of 30% colorectal cancer cells is actually an amino acid
The "life gate" of 30% colorectal cancer cells is actually an amino acid July 27, 2016 Source: WuXi PharmaTech Colorectal cancer is one of the most common types of cancer in China. There are more than 3 million new cases every year, and the population has shown a trend of rejuvenation in recent years, becoming a public health problem that needs to be addressed. Recently, scientists from Chinese and American research institutions such as Case Western Reserve University and Third Military Medical University have found that a considerable part of colon cancer has a special "hobby" for glutamine, which is not necessary for this kind. Amino acids have a higher demand than other cells. However, hobbies tend to become a person's weakness and even a "life gate", as well as cancer cells. Researchers believe that this weakness of cancer cells may become the next effective drug target for the treatment of colorectal cancer. This work was published in the recent Nature issue of Nature Communications. It turns out that this kind of colon cancer cells with special preference for glutamine carry the PIK3CA gene mutation, which is widely present in many types of tumors, including about 30% colon cancer cells. This gene encodes the catalytic subunit p110α of phosphatidylinositol 3-kinase (P13K). P13K plays an important role in the regulation of cell proliferation, survival and metastasis. Once activated, it activates the classical signaling pathways such as PI3K-Akt and has a wide-ranging effect on cells. This mutated p110α will eventually lead to a significant increase in alanine aminotransferase 2 (GPT2) expression, whereas glutamine is the substrate for GPT2. In fact, glutamine has an unusual meaning for cancer cells. Unlike normal cells, glucose taken up by cancer cells is mainly decomposed into lactic acid by the glycolysis pathway to produce energy, even in the presence of oxygen. Glutamine, on the other hand, is often the starting point for the tricarboxylic acid (TCA) cycle in cancer cells, which is converted to alpha-ketoglutarate (αKG) by three enzymes, including alanine aminotransferase (GPT). Then officially enter the TCA cycle. In cancer cells with PIK3CA gene mutations, the demand for glutamine is greatly increased due to the abnormally elevated GPT2 activity, which has become the "life gate" of these cancer cells. When the researchers stopped supplying glutamine to cancer cells carrying the PIK3CA gene mutation in vitro, these cancer cells could not stand the test and died, while cancer cells without the mutation were not affected. Moreover, when the investigator injected aminooxyacetate into a mouse model of colorectal cancer with a PIK3CA gene mutation, tumor growth was inhibited. Aminooxyacetic acid is a small molecule inhibitor of various transaminase including GPT2. "We will be based on this discovery to launch a clinical trial of colorectal cancer at the University Hospitals Seidman Cancer Center this summer," said NealMeropol, one of the authors of the Seidman Cancer Center. In this clinical trial led by him, the researchers will test the efficacy of a certain glutamate metabolism inhibitor in patients with advanced colorectal cancer. Food Grade Gelatin,Food Additives Gelatin,Bovine Gelatin Powder,Edible Gelatin Powder Hebei Haodong Biological Technology Co.,Ltd. , https://www.hdgelatin.com