Acid-sensing ion channels contribute to the effect of extracellular acidosis on proliferation and migration of A549 cells

Abstract

Acid-sensing ion channels, a proton-gated cation channel, can be activated by low extracellular pH and involved in pathogenesis of some tumors such as glioma and breast cancer. However, the role of acid-sensing ion channels in the growth of lung cancer cell is unclear. In this study, we investigated the expression of acid-sensing ion channels in human lung cancer cell line A549 and their possible role in proliferation and migration of A549 cells. The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli. Moreover, we found that acidic extracellular medium or overexpressing acid-sensing ion channel 1a promotes proliferation and migration of A549 cells. In addition psalmotoxin 1, a specific acid-sensing ion channel 1a inhibitor, or acid-sensing ion channel 1a knockdown can abolish the effect of acid stimuli on A549 cells. In addition, acid-sensing ion channels mediate increase of [Ca] induced by low extracellular pH in A549 cells. All these results indicate that acid-sensing ion channel-calcium signal mediate lung cancer cell proliferation and migration induced by extracellular acidosis, and acid-sensing ion channels may serve as a prognostic marker and a therapeutic target for lung cancer.

Retracted Article: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells

“…In fact, ASIC1a can work via adjusting intracellular Ca 2+ concentration, which has been reported by a lot of literatures. 9,11,14,26,27 Ca 2+ serves as one of the most important second messengers regulating many important cellular functions, and it may have a positive effect on the expression of ASIC1a and activation and autophagy of PSCs. So, once ASIC1a is blocked, ASIC1a-mediated Ca 2+ inux response to acid stimulation is limited, and the downstream processes are affected accordingly.…”

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…On the contrary, antidiabetic drugs of the sulfonylurea family, known to stimulate the pancreatic secretion of INS, appear to have a negative impact on BC growth, also increasing BC risk [ 148 , 149 , 150 ]. Furthermore, the overexpression of insulin and/or the insulin growth factor 1 gene are associated with a decrease in the length of the life of women with BC, while their suppression increases life span and decreases tumorigenesis [ 28 , 103 , 142 , 143 , 145 , 146 , 147 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ]. Hyperinsulinemia has also been considered an important factor in a wide array of human malignancies, while insulin inhibition has been proposed to decrease their growth [ 158 , 159 ].…”

“…VGSC, mainly Na(v)1.5 sodium channels, have become a relevant therapeutic target in cancer [ 157 ] since they promote cancer growth and invasion in BC [ 92 , 109 , 186 ]. Na(v)1.5 inhibition has been reported to increase survival in patients with BC [ 4 , 236 ].…”

Towards An Integral Therapeutic Protocol for Breast Cancer based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…On the contrary, antidiabetic drugs of the sulfonylurea family, known to stimulate the pancreatic secretion of INS, appear to have a negative impact on BC growth, also increasing BC risk [137][138][139]. Furthermore, the overexpression of INS and/or the IGF-1 gene are associated with a decrease in the length of life of women with BC, while their suppression increases life span and decreases tumorigenesis [27,91,131,132,[134][135][136][140][141][142][143][144][145][146]. Hyperinsulinemia has also been considered an important factor in a wide array of human malignancies, while insulin inhibition has been proposed to decrease their growth [147,148].…”