Fig. 2

Important Ca²⁺ channels/transporters in multiple myeloma cells. ER: Endoplasmic reticulum; OMM: Outernal mitochondrial membranes; IMM: internal mitochondrial membranes. The intracellular Ca²⁺ is governed by a series of proteins: (1) plasma membrane Ca²⁺ channels or transporters, such as TRPs (TRPV1, TRPV2, TRPV4, TRPM7), G Protein-Coupled Receptors (CaSR, CTR, PTH-R1), Purinergic receptors (P2X7), which mediate Ca²⁺ influx into cells. (2) Store-Operated Ca²⁺ Entry, as one of the major pathways for Ca²⁺ influx across plasma membrane. (3) Mitochondrial Ca²⁺ transporters, including VDAC1 and MCU, mediate Ca²⁺ transport across internal and outernal mitochondrial membranes. (4) Ca²⁺-ATPases pumping Ca²⁺ from cytosol to extracellular space. Ca²⁺ can regulate various cellular events, including gene transcription, proliferation, migration and apoptosis. During development of multiple myeloma, the alteration of Ca²⁺ channels/transporters lead to changes in Ca²⁺ permeability and distribution inside and outside the cell membrane as well as activation of various signaling pathways, providing a suitable microenvironment for the growth of tumor cells. Targeting the dysregulated Ca²⁺ channels/transporters may improve the prognosis of patients with MM