Pathophysiological role of calcium channels and transporters in the multiple myeloma

Li, Tingting; Chen, Junmin; Zeng, Zhiyong

doi:10.1186/s12964-021-00781-4

Cell Communication and Signaling

Table 1 Expression, localization and phthophysiological function of calcium channels and transporters in MM

From: Pathophysiological role of calcium channels and transporters in the multiple myeloma

Name	Related channels/transporters	Main localization	Compound	Mechanism	Pathophysiological role in MM	References
TRPVs	TRPV1	Plasma membrane	Capsaicin	Activator	TRPV1 inhibitor has synergistic anti-MM activity with bortezomib	[47]
	TRPV2	Plasma membrane	SKF96365	Inhibitor	TRPV2 promotes osteoclast differentiation	[13]
	TRPV4	Plasma membrane	–	–	TRPV4 activation promotes osteoclast differentiation and bone resorption	[60]
TRPMs	TRPM7	Plasma membrane	–	–	TRPM7 regulates MM cell motility and dissemination	[68]
GPCRs	CaSR	Plasma membrane	CaCl₂ Gadolinium Neomycin	Activator Activator Activator	CaSR promotes the mitosis of MM cells	[57]
	CTR	Plasma membrane	Calcitonin	Activator	CTR inhibits bone resorption by neutralizing OC migration and shape retraction, and may participate in the osteoclast differentiation of MM	[85] [89]
	PTH-R1	Plasma membrane	PTHrP	Activator	PTHrP stimulates the secretion of PTH-R1, promotes proliferation of MM cells and the production of osteoclastogenesis factors	[90] [92]
Purinergic receptors	P2X7	Plasma membrane	ATP	Activator	Activation of P2X7 may induce the apoptosis and prevent the proliferation of MM cells	[15]
SOCE	Stim1	Plasma membrane,	SKF-96365 DES 2-APB	Inhibitor Inhibitor Inhibitor	Silencing Stim1 reduces cell viability, leading to apoptosis and cell cycle arrest of MM cells, and the high expression of Stim1 affects the clinical outcome of MM. In addition, Stim1 could regulate the motility and dissemination of diffuse large B-cell lymphoma (DLBCL) cells and MM cells	[16] [68] [126]
		Endoplasmic reticulum
	Orai1	Plasma membrane,	SKF-96365 DES 2-APB	Inhibitor Inhibitor Inhibitor	Silencing Orai1 reduces cell viability, leading to apoptosis and cell cycle arrest of MM cells. And Orai1 regulates the motility and dissemination of diffuse large B-cell lymphoma (DLBCL) cells and MM cells	[16] [68] [111] [126]
		Cytosol	AnCoA4
	TRPC1	Plasma membrane	–	–	Knockout of TRPC1 inhibits the death of MM cells	[132]
Mitochondrial Ca²⁺ transporters	VDAC1	Mitochondrion, Nucleus	–	–	VDAC1 promotes the growth of MM cells, accelerates the development of MM, and affects the prognosis of patients	[17] [144]
Mitochondrial Ca²⁺ transporters	MCU	Mitochondrion	Ruthenium red	Inhibitor	MCU can reduce MM bortezomib resistance and promote MM cell apoptosis	[151] [152]

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ISSN: 1478-811X

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