ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca2+ /RhoA pathway

Cell Death & Disease
Shuai ZhuGang Zhao

Abstract

Extracellular acid can have important effects on cancer cells. Acid-sensing ion channels (ASICs), which emerged as key receptors for extracellular acidic pH, are differently expressed during various diseases and have been implicated in underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca2+ concentration ([Ca2+]i). Inhibition of ASIC1 and ASIC3 with siRNA or pharmacological inhibitor significantly decreased [Ca2+]i and its downstream RhoA during acidity and, thus, suppressed acidity-induced epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. Meanwhile, downregulating [Ca2+]i with calcium chelating agent BAPTA-AM or knockdown of RhoA with siRNA also significantly repressed acidity-induced EMT of pancreatic cancer cells. Significantly, although without obvious effect on proliferation, knockdown of ASIC1 and ASIC3 in pancreatic cancer cells significantly suppresses liver and lung metastasis in xenograft model. In addition, ASIC1 and ASIC3 are positively correlated with expression...Continue Reading

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Citations

May 16, 2019·Cold Spring Harbor Perspectives in Biology·Sarah J Roberts-ThomsonGregory R Monteith
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Jul 22, 2021·The FEBS Journal·Ling WuLiang Zhao

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Methods Mentioned

BETA
xenografts
GTPase
pancreatectomy
biopsy
transfection
electrophoresis

Software Mentioned

TILL
SPSS
Pulse
PulseFit

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