Description
Ammonia is broadly known as a common metabolic waste product in biology. Abnormal ammonia accumulation will eventually direct to apoptosis, but in some special cases, such as in the tumour microenvironment, ammonia accumulation is contributory to tumourigenesis. Here, we attempted to illustrate ammonia accumulation-induced activation of the mTORC2/Akt pathway and proliferation of hepatocellular carcinoma cells. Our results indicate that this activation is likely caused by ammonia-induced calcium accumulation as the depletion of intracellular Ca2+ using the Ca2+ chelator BAPTA-AM inhibited mTORC2 activation at high ammonia concentrations. The sodium-calcium exchanger (NCX) is a Ca2+ channel protein that is widely and highly expressed in cardiomyocytes, neuronal cells, and other cells with significant membrane potential changes. In this work, we demonstrated the potential role of its reverse mode in the setting of hepatocellular carcinoma with ammonia excess and find that activation of the mTORC2/Akt pathway is suppressed to a certain extent either by KB-R7943 treatment, an NCX reverse mode-specific inhibitor, or by siSLC8A1-induced knockdown. This signaling cascade, which has not yet been clearly described, may be able to suggest a new way of reviewing and research directions in the field of hepatocellular carcinoma and ammonia metabolism.| Period | 1 Sept 2023 → 10 Jun 2024 |
|---|---|
| Degree of Recognition | National |