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Lactic acid plays a crucial role in tumor growth
Lactic acid (lactate) is involved in numerous biochemical and cellular processes. For example, if the body does not have enough oxygen, anaerobic energy production produces lactic acid, which acidifies the muscle. As early as 1913, the researcher Otto Warburg discovered that various cancer cells produce large amounts of lactate even with an adequate oxygen supply. This discovery, known as the "Warburg Effect", was awarded a Nobel Prize. Over 100 years later, a research team has now deciphered the exact functional mechanism behind the Warburg effect, opening up new approaches to combating cancer.
Researchers at the University of Bern are the first to describe a transport cycle for cancer cells that secures the survival of the tumor and promotes its growth. Lactic acid plays a crucial role in this. Apparently, certain tumor cells use anaerobic energy generation to meet their high energy requirements. This creates a large amount of lactate. As the Bern research team has now discovered, the tumor cells use special transport proteins to discharge the lactate. The removal not only ensures the survival of the cancer cells, but also acidifies the area surrounding the tumor, thereby promoting its growth. The study results were recently presented in the renowned journal "Nature Communications".
Lactate circulation supplies cancer cells with energy
According to the Bern research team, certain cancer cells rely on the removal of large amounts of lactate to ensure that the cells survive. For this they use a transport protein called "Monocarboxylate Transporter 4" (MCT4). The protein is embedded in the cell membrane and transports the lactate from "inside" to "outside". According to the researchers, this causes the area surrounding the cancer cell to be acidified, which stimulates the growth and metastasis of the tumor. The removed lactate is then taken up by another transport protein called MCT1 and re-introduced into other cancer cells, where it serves as food for the cells.
Block cancer cell transport routes
A promising approach is therefore to block the transport routes of the lactate by inhibiting the MCT1 and MCT4 proteins. So far, however, no such inhibitors have been approved on the market. "In order to develop such effective and highly specific inhibitors, detailed knowledge of the structure of MCT1 and MCT4 is required," explains research director Dimitrios Fotiadis from the Institute of Biochemistry and Molecular Medicine (IBMM). The exact structure of these transport proteins was previously unknown. The Bern team has now succeeded in decoding and documenting the exact structure. This laid the foundation for the development of targeted inhibitors to block the cancer transport routes.
Possible points of attack identified
"The decoded structure together with our detailed transport study can now help to develop drugs based on model structures of MCT1 and MCT4," summarizes the study director. In addition, the team also discovered a possible docking site on the outside of the protein that could serve as a target for active ingredients. This is of great importance from a pharmacological point of view, since it will enable future inhibitors to be tested much more quickly. (vb)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Graduate editor (FH) Volker Blasek
Swell:
- University of Bern: Fighting cancer: structure of important transport protein decoded, (accessed: June 22, 2019), unibe.ch
- Bosshart, Patrick D. / Kalbermatter, David / Bonetti, Sara / Fotiadis, Dimitrios: Mechanistic basis of L-lactate transport in the SLC16 solute carrier family, Naure Communications, (access: June 22, 2019), nature.com
