NFATc2 enhances tumor-initiating phenotypes through the NFATc2/SOX2/ALDH axis in lung adenocarcinoma

摘要

Cancer develops when cells become faulty and start to grow uncontrollably. They eventually form lumps or tumors, which may spread to surrounding tissues or even to other areas in the body. One of the reasons why cancer treatment remains a challenge is that there are over 200 types of cells in the body, and there are a lot of moments in the life cycle of a cell when things could go wrong. Researchers have shown that many cancers, including lung cancer, are not only extremely different from patient to patient, but also display great differences between cancer cells within the same tumor. Increasing evidence suggest that these differences may be caused by a type of cells called tumor initiating cells, or TICs for short. These TICs behave like stem cells and can renew themselves or mature into different types of cells. They are thought to help cancers grow and spread, and even make them resistant to treatments. Previous research has shown that in many types of cancer, the protein NFATc2 helps cancer cells to grow and spread. Until now, however, it was not known if NFATc2 is also important in TICs in lung cancer. Using human lung cancer cell lines and animal models, Xiao et al. show that the protein NFATc2 stimulates the stem-cell like behavior of TICs. The results showed that TICs had higher levels of the NFATc2 protein than other lung cancer cells that were not TICs. Tumors with higher levels were also more aggressive. When NFATc2 was removed from the cells, they formed smaller tumors and were more sensitive to drug treatment compared to cancer cells with NFATc2. Further experiments revealed that NFATc2 helped to increase the levels of a protein called Sox2, which gives cells the ability to renew or develop into different cell types. Together, these two proteins stimulated the production of another protein that was already known to play a crucial role in TIC maintenance. A better understanding of the mechanisms regulating TICs in lung cancer will help scientists tackle new questions about how this cancer progresses and resists to therapy. In the longer-term, combining classic cancer treatments with new therapeutic strategies targeting NFATc2 could make treatments for lung cancer patients more effective.