Endoplasmic Reticulum Calcium Pumps and Tumor Cell Differentiation.

Abstract

Endoplasmic reticulum (ER) calcium homeostasis plays an essential role in cellular calcium signaling, intra-ER protein chaperoning and maturation, as well as in the interaction of the ER with other organelles. Calcium is accumulated in the ER by sarco/endoplasmic reticulum calcium ATPases (SERCA enzymes) that generate by active, ATP-dependent transport, a several thousand-fold calcium ion concentration gradient between the cytosol (low nanomolar) and the ER lumen (high micromolar). SERCA enzymes are coded by three genes that by alternative splicing give rise to several isoforms, which can display isoform-specific calcium transport characteristics. SERCA expression levels and isoenzyme composition vary according to cell type, and this constitutes a mechanism whereby ER calcium homeostasis is adapted to the signaling and metabolic needs of the cell, depending on its phenotype, its state of activation and differentiation. As reviewed here, in several normal epithelial cell types including bronchial, mammary, gastric, colonic and choroid plexus epithelium, as well as in mature cells of hematopoietic origin such as pumps are simultaneously expressed, whereas in corresponding tumors and leukemias SERCA3 expression is selectively down-regulated. SERCA3 expression is restored during the pharmacologically induced differentiation of various cancer and leukemia cell types. SERCA3 is a useful marker for the study of cell differentiation, and the loss of SERCA3 expression constitutes a previously unrecognized example of the remodeling of calcium homeostasis in tumors.

• Authors: Bela Papp, Sophie Launay, Pascal Gélébart, Atousa Arbabian, Agnes Enyedi, Jean-Philippe Brouland, Edgardo D Carosella, Homa Adle-Biassette
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 9 (May 09 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32397400 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers, Tumor
• Isoenzymes
• Neoplasm Proteins
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• ATP2A3 protein, human
• Calcium

Topics

• Biomarkers, Tumor (analysis)
• Breast Neoplasms (enzymology)
• Calcium (metabolism)
• Calcium Signaling
• Carcinoma (enzymology)
• Cell Differentiation
• Cell Line, Tumor
• Choroid Plexus Neoplasms (enzymology)
• Endoplasmic Reticulum (metabolism)
• Gastrointestinal Neoplasms (enzymology)
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Homeostasis
• Humans
• Isoenzymes (genetics, metabolism)
• Leukemia, Promyelocytic, Acute (metabolism)
• Lung Neoplasms (enzymology)
• Megakaryocytes (cytology, metabolism)
• Neoplasm Proteins (metabolism)
• Neoplasms (metabolism)
• Organ Specificity
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (analysis, genetics, metabolism)