Ca²⁺ Transportome and the Interorganelle Communication in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a type of liver cancer with a poor prognosis for survival given the complications it bears on the patient. Though damages to the liver are acknowledged prodromic factors, the precise molecular aetiology remains ill-defined. However, many genes coding for proteins involved in calcium (Ca²⁺) homeostasis emerge as either mutated or deregulated. Ca²⁺ is a versatile signalling messenger that regulates functions that prime and drive oncogenesis, favouring metabolic reprogramming and gene expression. Ca²⁺ is present in cell compartments, between which it is trafficked through a network of transporters and exchangers, known as the Ca²⁺ transportome. The latter regulates and controls Ca²⁺ dynamics and tonicity. In HCC, the deregulation of the Ca²⁺ transportome contributes to tumorigenesis, the formation of metastasizing cells, and evasion of cell death. In this review, we reflect on these aspects by summarizing the current knowledge of the Ca²⁺ transportome and overviewing its composition in the plasma membrane, endoplasmic reticulum, and the mitochondria.