. 2024 Mar 5;12:1326231. doi: 10.3389/fcell.2024.1326231

TABLE 2.

Ca²⁺ signaling regulation by acidic pHe.

Ion channels/Receptors	Cell type	Effect of acidic pH on Channel’s/Receptors’ activity/Expression	Effect on Ca²⁺ signals		Effects on the tumor cells	Refs
ASICs	Breast cancer	Acidic microenvironment activates ASIC1/Ca²⁺ influx/[Ca²⁺]_i ↑/AKT/NF-κB/ROS			Inflammation	Gupta et al. (2016)
ASICs	Pancreatic Cancer	Acidic microenvironment activates ASIC1 and ASIC3/Ca²⁺ influx/[Ca²⁺]_i ↑/RhoA			Migration	Zhu et al. (2017)
TRPV1	HEK-293	E600 and E648 are key sites in the enhancement and activation of acid-induced channels mediated by TRPV1	Not assessed			Zhang et al. (2021)
	Dorsal Root Ganglion (DRG) Neurons	Mild acidosis activate TRPV1/Ca²⁺ influx/[Ca²⁺]i ↑				Heber et al. (2020)
	Synoviocytes	Acidic solution activate TRPV1/Ca²⁺ influx/[Ca²⁺]i ↑/ROS			Inflammation	Hu et al. (2008)
	PC-3	Not assessed	Ca²⁺/ERK1/2		Proliferation	Morelli et al. (2014)
	LNCaP	Not assessed	Ca²⁺/PI3K		Proliferation, Migration	Malagarie-Cazenave et al. (2009)
	LNCaP	Not assessed	Ca²⁺/ERK1/2		Proliferation, Migration	Malagarie-Cazenave et al. (2009)
	Colon cancer	Not assessed	Ca²⁺/NF-kB		Inflammation	Vinuesa et al. (2012)
	Colon cancer	Not assessed	Ca²⁺/STAT3		Inflammation	Vinuesa et al. (2012)
TRPV4	HEK-293	TRPV4 is gated by a drop of pH below 6 and the channel current reaches a maximum at a pH of about 4	Not assessed			Holzer (2011)
TRPV4	Endometrial carcinoma	Not assessed	Ca²⁺/RhoA/ROCK1		Migration	Li et al. (2020)
TRPC1-TRPC4-TRPC5	HEK-293	The effects of changes in pH on TRPC4 and TRPC5 activity are the currents being increased by a reduction of pH down to about 6.5	Not assessed			Semtner et al. (2007)
	MDCK-F cell	Not assessed	Ca²⁺/MAPK Ca²⁺/PI3K/AKT		Migration, Proliferation	Fabian et al. (2008)
	MCF-7/ADM	Not assessed	Ca²⁺/CaMKKβ/AMPKA/mTOR		Proliferation	Zhang et al. (2017)
	CRC	Not assessed	Ca²⁺/β-catenin/ABCB1		Drug Resistance	Wang et al. (2015c)
TRPP2	HEK-293	TRPP2 is sensitive to acidic microenvironments	Not assessed			Holzer (2011)
TRPP2	Hep2cell	Not assessed	Ca²⁺/CaMKKβ/AMPK/PERK/eIF2α		Migration	Liang et al. (2008), Wu et al. (2016)
VGCC	Melanoma	extracellular acidic pH/Ca²⁺ influx/[Ca²⁺]i ↑/NF-kB			Migration, Inflammation	Kato et al. (2007)
P2X2	HEK-293	Acidic microenvironment activates P2X2/Ca²⁺ influx/[Ca²⁺]i ↑				King et al. (1997), He et al. (2003), Stojilkovic et al. (2014)
P2X2	Walker 256	Not assessed	Ca²⁺/NF-kB		Migration, Inflammation	Zhang et al. (2020)
SOCC	HEK-293	Proton-sensing GPCRs activate SOCC through the PLC/IP3/IP3R signaling pathway	Not assessed			Wiley et al. (2019), Haque et al. (2020)
	Pancreatic stellate cells	Not assessed	Ca²⁺/AKT		Proliferation	Radoslavova et al. (2021)
	Breast cancer	Not assessed	Ca²⁺/PI3K/AKT/SgK1		Proliferation	Hasna et al. (2018)
	LCSC	Not assessed	Ca²⁺/CaN/NFAT		Drug Resistance	Wang et al. (2021)
OGR1	Medulloblastoma	human cerebellar granule cell tumor (medulloblastoma) cell line (DAOY) showed high levels of expression of the OGR1 and G2A, Extracellular Acidification/PLC/IP3/IP3R/[Ca²⁺]i ↑/MEK/ERK			Proliferation	Huang et al. (2008)
GPR4	Neuroblastoma (SH-SY5Y)	GPR4 mRNA expression was increased at both pH 6.4 and 7.4		Not assessed		Haque et al. (2020)
GPR4	Neuroblastoma (SH-SY5Y)	Not assessed		H₂O₂/GPR4/Gq/PLC/IP3/IP3R/[Ca²⁺]i ↑/ROS	Inflammation	Haque et al. (2020)
TDAG8	HEK-293	TDAG8 regulates TRPV1 in acidic environments/[Ca²⁺]i ↑				Lin et al. (2017)
G2A	HEK-293	Co-expression of OGR1 and G2A promotes proton sensitivity and calcium influx and ER calcium release, G2A alone could not induce an increase in intracellular calcium concentration				Huang et al. (2016)