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Genovese et al. Cancer Drug Resist 2018;1:164-80 Cancer
DOI: 10.20517/cdr.2018.10 Drug Resistance

Review Open Access

Molecular bases of Sorcin-dependent resistance to
chemotherapeutic agents

Ilaria Genovese , Andrea Ilari , Theo Battista , Valerio Chiarini , Francesco Fazi , Annarita Fiorillo ,
3
5
4
3
1
2
Gianni Colotti 2
1 Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Rome 00161, Italy.
2 IBPM-CNR, Institute of Molecular Biology and Pathology, Italian National Research Council, Rome 00185, Italy.
3 Department of Biochemical Sciences, Sapienza University of Rome, Rome 00185, Italy.
4 Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
5 Department of Anatomical, Histological, Forensic Medicine & Orthopedic Sciences, Sapienza University of Rome, laboratory
affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome 00161, Italy.
Correspondence to: Dr. Andrea Ilari, IBPM-CNR, Institute of Molecular Biology and Pathology, Italian National Research Council,
Rome 00185, Italy. E-mail: andrea.ilari@uniroma1.it; Dr. Gianni Colotti, IBPM-CNR, Institute of Molecular Biology and Pathology,
Italian National Research Council, Rome 00185, Italy. E-mail: gianni.colotti@uniroma1.it
How to cite this article: Genovese I, Ilari A, Battista T, Chiarini V, Fazi F, Fiorillo A, Colotti G. Molecular bases of Sorcin-dependent
resistance to chemotherapeutic agents. Cancer Drug Resists 2018;1:164-80. http://dx.doi.org/10.20517/cdr.2018.10
Received: 28 Jun 2018 First Decision: 9 Aug 2018 Revised: 16 Aug 2018 Accepted: 20 Aug 2018 Published: 19 Sep 2018

Science Editors: Elisa Giovannetti, Jose Antonio Rodriguez Copy Editor: Yuan-Li Wang Production Editor: Cai-Hong Wang

Abstract
Soluble resistance-related calcium binding protein (Sorcin) is a protein initially labelled “resistance-related”, since it is
co-amplified with ABCB1 in multidrug (MD)-resistant cells. While for years Sorcin overproduction was believed to be
a by-product of the co-amplification of its gene with the P-glycoprotein gene, many recent studies view Sorcin as an
oncoprotein, playing an important role in MD resistance (MDR). Sorcin is one of the most highly expressed calcium-
binding proteins, which is overexpressed in many human tumors and MD resistant cancers, and represents a novel
MDR marker. Sorcin expression in tumors inversely correlates with patients’ response to chemotherapies and overall
prognosis. Sorcin is highly expressed in MDR cell lines over their parent cells. Sorcin overexpression by gene transfection
increases drug resistance to a variety of chemotherapeutic drugs in many cancer lines. On the other hand, Sorcin
silencing leads to reversal of drug resistance in many cell lines. This review describes: (1) the roles of Sorcin in the cell;
(2) the studies showing Sorcin overexpression in tumors and cancer cells; (3) the studies showing the effects of Sorcin
overexpression and silencing; (4) the molecular effects of Sorcin overexpression; and (5) the structural and genetic
bases of Sorcin-dependent MDR.

Keywords: Sorcin, calcium, cancer, multidrug resistance in cancer, doxorubicin, endoplasmic reticulum, heart, brain,
ryanodine receptors, ER stress

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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