Ca Transportome and the Interorganelle Communication in Hepatocellular Carcinoma

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Mar 10

PMID 35269437

Authors

Hong-Toan Lai

Reynand Jay Canoy

Michelangelo Campanella

Yegor Vassetzky

Catherine Brenner

Affiliations

Soon will be listed here.

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 (Ca) homeostasis emerge as either mutated or deregulated. Ca is a versatile signalling messenger that regulates functions that prime and drive oncogenesis, favouring metabolic reprogramming and gene expression. Ca is present in cell compartments, between which it is trafficked through a network of transporters and exchangers, known as the Ca transportome. The latter regulates and controls Ca dynamics and tonicity. In HCC, the deregulation of the Ca 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 Ca transportome and overviewing its composition in the plasma membrane, endoplasmic reticulum, and the mitochondria.

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References

Lytton J . Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport. Biochem J. 2007; 406(3):365-82. DOI: 10.1042/BJ20070619. View

Jin M, Wang J, Ji X, Cao H, Zhu J, Chen Y . MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma. J Exp Clin Cancer Res. 2019; 38(1):136. PMC: 6434841. DOI: 10.1186/s13046-019-1135-x. View

Linck B, Qiu Z, He Z, Tong Q, Hilgemann D, Philipson K . Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3). Am J Physiol. 1998; 274(2):C415-23. DOI: 10.1152/ajpcell.1998.274.2.C415. View

El-Serag H . Hepatocellular carcinoma. N Engl J Med. 2011; 365(12):1118-27. DOI: 10.1056/NEJMra1001683. View

Lanner J, Georgiou D, Joshi A, Hamilton S . Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol. 2010; 2(11):a003996. PMC: 2964179. DOI: 10.1101/cshperspect.a003996. View

Wang C, Jacewicz A, Delgado B, Baradaran R, Long S . Structures reveal gatekeeping of the mitochondrial Ca uniporter by MICU1-MICU2. Elife. 2020; 9. PMC: 7434445. DOI: 10.7554/eLife.59991. View

Paupe V, Prudent J, Dassa E, Zurita Rendon O, Shoubridge E . CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter. Cell Metab. 2015; 21(1):109-16. DOI: 10.1016/j.cmet.2014.12.004. View

Huang G, Vercesi A, Docampo R . Essential regulation of cell bioenergetics in Trypanosoma brucei by the mitochondrial calcium uniporter. Nat Commun. 2013; 4:2865. PMC: 3868461. DOI: 10.1038/ncomms3865. View

Qi H, Li L, Shuai J . Optimal microdomain crosstalk between endoplasmic reticulum and mitochondria for Ca2+ oscillations. Sci Rep. 2015; 5:7984. PMC: 4303883. DOI: 10.1038/srep07984. View

10.

Soeller C, Crossman D, Gilbert R, Cannell M . Analysis of ryanodine receptor clusters in rat and human cardiac myocytes. Proc Natl Acad Sci U S A. 2007; 104(38):14958-63. PMC: 1986595. DOI: 10.1073/pnas.0703016104. View

11.

Lopez-Colome A, Lee-Rivera I, Benavides-Hidalgo R, Lopez E . Paxillin: a crossroad in pathological cell migration. J Hematol Oncol. 2017; 10(1):50. PMC: 5316197. DOI: 10.1186/s13045-017-0418-y. View

12.

Brereton H, Harland M, Froscio M, Petronijevic T, Barritt G . Novel variants of voltage-operated calcium channel alpha 1-subunit transcripts in a rat liver-derived cell line: deletion in the IVS4 voltage sensing region. Cell Calcium. 1997; 22(1):39-52. DOI: 10.1016/s0143-4160(97)90088-9. View

13.

Sander P, Gudermann T, Schredelseker J . A Calcium Guard in the Outer Membrane: Is VDAC a Regulated Gatekeeper of Mitochondrial Calcium Uptake?. Int J Mol Sci. 2021; 22(2). PMC: 7833399. DOI: 10.3390/ijms22020946. View

14.

De Marchi U, Santo-Domingo J, Castelbou C, Sekler I, Wiederkehr A, Demaurex N . NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby limiting Ca2+-induced NAD(P)H production and modulating matrix redox state. J Biol Chem. 2014; 289(29):20377-85. PMC: 4106350. DOI: 10.1074/jbc.M113.540898. View

15.

Delgado-Coello B, Santiago-Garcia J, Zarain-Herzberg A, Mas-Oliva J . Plasma membrane Ca2+-ATPase mRNA expression in murine hepatocarcinoma and regenerating liver cells. Mol Cell Biochem. 2003; 247(1-2):177-84. DOI: 10.1023/a:1024119831983. View

16.

Karacicek B, Erac Y, Tosun M . Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells. BMC Cancer. 2019; 19(1):751. PMC: 6668110. DOI: 10.1186/s12885-019-5947-z. View

17.

Burdakov D, Petersen O, Verkhratsky A . Intraluminal calcium as a primary regulator of endoplasmic reticulum function. Cell Calcium. 2005; 38(3-4):303-10. DOI: 10.1016/j.ceca.2005.06.010. View

18.

Rochette L, Meloux A, Zeller M, Malka G, Cottin Y, Vergely C . Mitochondrial SLC25 Carriers: Novel Targets for Cancer Therapy. Molecules. 2020; 25(10). PMC: 7288124. DOI: 10.3390/molecules25102417. View

19.

Lin L, Yan L, Liu Y, Qu C, Ni J, Li H . The Burden and Trends of Primary Liver Cancer Caused by Specific Etiologies from 1990 to 2017 at the Global, Regional, National, Age, and Sex Level Results from the Global Burden of Disease Study 2017. Liver Cancer. 2020; 9(5):563-582. PMC: 7548973. DOI: 10.1159/000508568. View

20.

Pierobon N, Renard-Rooney D, Gaspers L, Thomas A . Ryanodine receptors in liver. J Biol Chem. 2006; 281(45):34086-95. DOI: 10.1074/jbc.M607788200. View