Retracted Article: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells

Abstract

Acid-sensing ion channel 1a (ASIC1a) is expressed in pancreatic stellate cells and is involved in acidosis-induced activation and autophagy.

ASIC1 inhibition impairs the proliferation and migration of pancreatic stellate cells induced by pancreatic cancer cells

“…As shown in Figure 1B, the interaction caused ASIC1 expression increase in a time-dependent manner in both Panc-1 cells and PSCs, meaning that the malignant features of tumor were reinforced. It has been reported that an acidic environment can up-regulate ASIC1 expression in liver cancer cells, hepatic stellate cells and PSCs [10,11], but our results indicates that, besides acidity, pancreatic cancer cells and PSCs can promote ASIC1 expression for each other, despite through an uncertain mechanism.…”

“…PSCs, and the patients with a higher expression of ASIC1 have worse tumor differentiation, advanced TNM stage, lymph and distant metastasis, highlighting the potential value of ASIC1 as thermotic target of pancreatic cancer [8,11]. It is interesting to investigate the change of ASIC1 expression in cancer cells and PSCs after an in-direct co-culture.…”

“…ASIC1 belongs to one of proton-gated ion channels, and is mainly expressed in the mammalian nervous system and several digestive system tumors such as pancreatic cancer, gastric cancer, hepatocellular cancer [7][8][9]. Interestingly, ASIC1 expression also occur in hepatic stellate cells and PSCs, and it mediates acidosis-induced fibrosis, a common non-physiological wound-healing process in liver and pancreatic diseases [10,11]. In particular, ASIC1 regulates the acidity-induced epithelial mesenchymal transition (EMT) of pancreatic cancer cells and activation and autophagy of PSCs, and its expression level is inversely correlated with the tumor prognosis, suggesting its targeting value in pancreatic cancer treatment [8,11].…”

“…Interestingly, ASIC1 expression also occur in hepatic stellate cells and PSCs, and it mediates acidosis-induced fibrosis, a common non-physiological wound-healing process in liver and pancreatic diseases [10,11]. In particular, ASIC1 regulates the acidity-induced epithelial mesenchymal transition (EMT) of pancreatic cancer cells and activation and autophagy of PSCs, and its expression level is inversely correlated with the tumor prognosis, suggesting its targeting value in pancreatic cancer treatment [8,11]. From the concerned results on the function of ASIC1 in pancreatic cancer, it can be inferred that ASIC1 not only is a receptor or responder of extracellular acidic pH, but also plays a certain special role in the interaction between cancer cells and PSCs.…”

Autophagy: A Key Player in Pancreatic Cancer Progression and a Potential Drug Target

“…These cellular mechanisms can influence PDAC within an acidic TME. There is also significant evidence that an acidic TME can maintain autophagic stimulation over extensive periods of time and is capable of sustaining tumor cell survival [ 218 , 219 , 220 ]. The specific mechanism involving the induction of autophagy under acidic conditions has not been entirely elucidated.…”