Targeting ca2+ signaling in the initiation, promotion and progression of hepatocellular carcinoma

Eunus S. Ali, Grigori Y. Rychkov, Greg J. Barritt

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Hepatocellular carcinoma (HCC) is a considerable health burden worldwide and a major contributor to cancer-related deaths. HCC is often not noticed until at an advanced stage where treatment options are limited and current systemic drugs can usually only prolong survival for a short time. Understanding the biology and pathology of HCC is a challenge, due to the cellular and anatomic complexities of the liver. While not yet fully understood, liver cancer stem cells play a central role in the initiation and progression of HCC and in resistance to drugs. There are approximately twenty Ca2+-signaling proteins identified as potential targets for therapeutic treatment at different stages of HCC. These potential targets include inhibition of the self-renewal properties of liver cancer stem cells; HCC initiation and promotion by hepatitis B and C and nonalcoholic fatty liver disease (principally involving reduction of reactive oxygen species); and cell proliferation, tumor growth, migration and metastasis. A few of these Ca2+-signaling pathways have been identified as targets for natural products previously known to reduce HCC. Promising Ca2+-signaling targets include voltage-operated Ca2+ channel proteins (liver cancer stem cells), inositol trisphosphate receptors, store-operated Ca2+ entry, TRP channels, sarco/endoplasmic reticulum (Ca2++Mg2+) ATP-ase and Ca2+/calmodulin-dependent protein kinases. However, none of these Ca2+-signaling targets has been seriously studied any further than laboratory research experiments. The future application of more systematic studies, including genomics, gene expression (RNA-seq), and improved knowledge of the fundamental biology and pathology of HCC will likely reveal new Ca2+-signaling protein targets and consolidate priorities for those already identified.

Original languageEnglish
Article number2755
Pages (from-to)1-33
Number of pages33
Issue number10
Publication statusPublished or Issued - Oct 2020


  • Ca, hepatocellular carcinoma
  • Cancer stem cells
  • Liver
  • Mitochondria
  • Reactive oxygen species
  • STIM1
  • TRP channels

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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