Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC
Calcium is the most abundant element in the human body. Its role is essential in physiological and biochemical processes such as signal transduction from outside to inside the cell between the cells of an organ, as well as the release of neurotransmitters from neurons, muscle contraction, fertilizat...
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doaj-0930f1de704741e2b74daa4b7d8717d92020-11-25T01:56:43ZengMDPI AGCancers2072-66942019-10-011110158810.3390/cancers11101588cancers11101588Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCCTeresa Maria Elisa Modica0Francesco Dituri1Serena Mancarella2Claudio Pisano3Isabel Fabregat4Gianluigi Giannelli5Department of Biomedical Science and Human Oncology, Università degli Studi di Bari Aldo Moro, 70121 Bari, ItalyIRCCS Saverio De Bellis Castellana Grotte, 70013 Bari, ItalyIRCCS Saverio De Bellis Castellana Grotte, 70013 Bari, ItalyBiogem S.C.A.R.L., 83031 Ariano Irpino (AV), ItalyBellvitge Biomedical Research Institute (IDIBELL) L’Hospitalet, 08907 Barcelona, SpainIRCCS Saverio De Bellis Castellana Grotte, 70013 Bari, ItalyCalcium is the most abundant element in the human body. Its role is essential in physiological and biochemical processes such as signal transduction from outside to inside the cell between the cells of an organ, as well as the release of neurotransmitters from neurons, muscle contraction, fertilization, bone building, and blood clotting. As a result, intra- and extracellular calcium levels are tightly regulated by the body. The liver is the most specialized organ of the body, as its functions, carried out by hepatocytes, are strongly governed by calcium ions. In this work, we analyze the role of calcium in human hepatoma (HCC) cell lines harboring a wild type form of the Epidermal Growth Factor Receptor (EGFR), particularly its role in proliferation and in EGFR downmodulation. Our results highlight that calcium is involved in the proliferative capability of HCC cells, as its subtraction is responsible for EGFR degradation by proteasome machinery and, as a consequence, for EGFR intracellular signaling downregulation. However, calcium-regulated EGFR signaling is cell line-dependent. In cells responding weakly to the epidermal growth factor (EGF), calcium seems to have an opposite effect on EGFR internalization/degradation mechanisms. These results suggest that besides EGFR, calcium could be a new therapeutic target in HCC.https://www.mdpi.com/2072-6694/11/10/1588hccegfr degradationazd9291calcium ionsbapta_am |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Teresa Maria Elisa Modica Francesco Dituri Serena Mancarella Claudio Pisano Isabel Fabregat Gianluigi Giannelli |
spellingShingle |
Teresa Maria Elisa Modica Francesco Dituri Serena Mancarella Claudio Pisano Isabel Fabregat Gianluigi Giannelli Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC Cancers hcc egfr degradation azd9291 calcium ions bapta_am |
author_facet |
Teresa Maria Elisa Modica Francesco Dituri Serena Mancarella Claudio Pisano Isabel Fabregat Gianluigi Giannelli |
author_sort |
Teresa Maria Elisa Modica |
title |
Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC |
title_short |
Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC |
title_full |
Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC |
title_fullStr |
Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC |
title_full_unstemmed |
Calcium Regulates HCC Proliferation as well as EGFR Recycling/Degradation and Could Be a New Therapeutic Target in HCC |
title_sort |
calcium regulates hcc proliferation as well as egfr recycling/degradation and could be a new therapeutic target in hcc |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-10-01 |
description |
Calcium is the most abundant element in the human body. Its role is essential in physiological and biochemical processes such as signal transduction from outside to inside the cell between the cells of an organ, as well as the release of neurotransmitters from neurons, muscle contraction, fertilization, bone building, and blood clotting. As a result, intra- and extracellular calcium levels are tightly regulated by the body. The liver is the most specialized organ of the body, as its functions, carried out by hepatocytes, are strongly governed by calcium ions. In this work, we analyze the role of calcium in human hepatoma (HCC) cell lines harboring a wild type form of the Epidermal Growth Factor Receptor (EGFR), particularly its role in proliferation and in EGFR downmodulation. Our results highlight that calcium is involved in the proliferative capability of HCC cells, as its subtraction is responsible for EGFR degradation by proteasome machinery and, as a consequence, for EGFR intracellular signaling downregulation. However, calcium-regulated EGFR signaling is cell line-dependent. In cells responding weakly to the epidermal growth factor (EGF), calcium seems to have an opposite effect on EGFR internalization/degradation mechanisms. These results suggest that besides EGFR, calcium could be a new therapeutic target in HCC. |
topic |
hcc egfr degradation azd9291 calcium ions bapta_am |
url |
https://www.mdpi.com/2072-6694/11/10/1588 |
work_keys_str_mv |
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