Acid sensor ASIC1a promotes malignant cell proliferation through the TCF7/c-Myc pathway in liver cancer.

Abstract

The extracellular acidic microenvironment plays a pivotal role in driving tumor initiation and sustaining its malignant progression. Therefore, understanding its regulatory mechanism is crucial for the treatment of liver cancer. Acid sensing ion channel 1a (ASIC1a) serves as the primary acid sensor, transmitting the extracellular low pH signal into the cell to initiate downstream signaling pathways. In this study, we have investigated the pathogenic role of ASIC1a in liver cancer and elucidated its molecular mechanism. Our findings suggest that ASIC1a facilitates the proliferation of liver cancer cells and enhances their malignant characteristics in the acidic microenvironment. Relevantly, this deleterious characteristic was notably repressed upon the inhibition of ASIC1a activity. Transcription factor 7 (TCF7) acts as a crucial mediator, transmitting the activation signals from ASIC1a to upregulate c-Myc expression, thereby promoting the proliferation of liver cancer cells. In conclusion, our results provide new insights into how the extracellular acidic microenvironment contributes to the advancement of liver cancer.