Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target
The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivatio...
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doaj-71b54641aaee4dd4ae8b804a69ee3a4e2020-11-25T02:26:48ZengMDPI AGCancers2072-66942020-04-011288788710.3390/cancers12040887Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug TargetTheo Battista0Annarita Fiorillo1Valerio Chiarini2Ilaria Genovese3Andrea Ilari4Gianni Colotti5Department of Biochemical Sciences, Sapienza University, P.le A.Moro 5, 00185 Rome, ItalyDepartment of Biochemical Sciences, Sapienza University, P.le A.Moro 5, 00185 Rome, ItalyDoctoral Programme in Integrative Life Science, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, FinlandDepartment of Medical Sciences, Laboratory for Technologies of Advanced Therapies, University of Ferrara, 44121 Ferrara, ItalyInstitute of Molecular Biology and Pathology, Italian National Research Council, Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche (IBPM-CNR), c/o Department of Biochemical Sciences, Sapienza University, P.le A.Moro 5, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology, Italian National Research Council, Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche (IBPM-CNR), c/o Department of Biochemical Sciences, Sapienza University, P.le A.Moro 5, 00185 Rome, ItalyThe development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules.https://www.mdpi.com/2072-6694/12/4/887sorcinABCB1multidrug resistancecancerschemotherapeutic drugscalcium |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Theo Battista Annarita Fiorillo Valerio Chiarini Ilaria Genovese Andrea Ilari Gianni Colotti |
spellingShingle |
Theo Battista Annarita Fiorillo Valerio Chiarini Ilaria Genovese Andrea Ilari Gianni Colotti Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target Cancers sorcin ABCB1 multidrug resistance cancers chemotherapeutic drugs calcium |
author_facet |
Theo Battista Annarita Fiorillo Valerio Chiarini Ilaria Genovese Andrea Ilari Gianni Colotti |
author_sort |
Theo Battista |
title |
Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target |
title_short |
Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target |
title_full |
Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target |
title_fullStr |
Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target |
title_full_unstemmed |
Roles of Sorcin in Drug Resistance in Cancer: One Protein, Many Mechanisms, for a Novel Potential Anticancer Drug Target |
title_sort |
roles of sorcin in drug resistance in cancer: one protein, many mechanisms, for a novel potential anticancer drug target |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-04-01 |
description |
The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules. |
topic |
sorcin ABCB1 multidrug resistance cancers chemotherapeutic drugs calcium |
url |
https://www.mdpi.com/2072-6694/12/4/887 |
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