Abstract
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.
Highlights
Liver cancer poses a major challenge to the national healthcare system of many countries, in east Asian countries [1,2]
We will discuss recent evidence revealing that some members of the Ca2+ transportome (i.e., mitochondrial Ca2+ uniporter (MCU), MCU regulator 1 (MCRU1), TRP cation channel subfamily C member 6 (TRPC6), and Stromal Interaction Molecule 1 (STIM1)) notably impact intracellular Ca2+ level, mitochondrial ROS production, and transcriptomic profiles, and how these deregulations promote Hepatocellular carcinoma (HCC) progression
It is the main compartment in which the majority of intracellular Ca2+ is stored, its Ca2+ content depending on the cooperation of various channels belonging to the endoplasmic reticulum plasmic reticulum (ER) Ca2+ transportome, such as the ryanodine receptor (RyR) and the IP3R as Ca2+ release channels, and the SERCA family for ER Ca2+ accumulation (Figure 1)
Summary
Liver cancer poses a major challenge to the national healthcare system of many countries, in east Asian countries [1,2]. As the third most common cause of death from cancer in the Asia–Pacific region, 72% of HCC cases can be found in Vietnam, China, North Korea, and South Korea [4] In these populations, the male-to-female ratio reaches up to 3:1, the HCC rate in men is three times higher than in women [5,6]. Early-stage (BCLC 0 and BCLC A) patients are eligible for conventional treatments, such as local ablation, surgical resection, or liver transplant [9,10] Another crucial clinical obstacle is that HCC is resistant to chemotherapy, due to multidrug resistance (MDR) mechanisms induced by conventional anticancer drugs. We will discuss recent evidence revealing that some members of the Ca2+ transportome (i.e., MCU, MCU regulator 1 (MCRU1), TRPC6, and STIM1) notably impact intracellular Ca2+ level, mitochondrial ROS (mtROS) production, and transcriptomic profiles, and how these deregulations promote HCC progression
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