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Genovese et al. Cancer Drug Resist 2018;1:164-80 I http://dx.doi.org/10.20517/cdr.2018.10 Page 171

Figure 5. Sorcin is able to bind with high affinity doxorubicin and other drugs: the crystal structure of the sorcin-doxorubicin complex
shows that the drug binds to the EF5 hand [87]

Table 1. Selected studies on the effects of sorcin overexpression and/or silencing in tumor cell lines

Tumor cell lines Resistance Overexpression (O), Reference
silencing (S)
Leukemia (K562), breast cancer (MCF-7) Doxorubicin O,S 22
Leukemia (K562) Doxorubicin O 69
Leukemia (K562) Doxorubicin, vincristine O,S 72
Leukemia (K562) Doxorubicin, etoposide, Homoharringtonine, O,S 74
vincristine
Lung adenocarcinoma (A549) Cisplatin S 75
Leukemia (K562), breast cancer (MCF-7) Adriamycin S 76
Leukemia (CCRF-CEM) Methotrexate O 77
Colorectal cancer (CRC) 5-fluorouracil, oxaliplatin, irinotecan O,S 78
Lung cancer (H1299) Doxorubicin O,S 87
Leukemia (K562) Adriamycin O 88
Gastric cancer (SGC7901) Vincristine, adriamycin, taxol, 5-fluorouracil O,S 89
Cervical carcinoma (HeLa) Vinblastine O,S 90
Nasopharingeal carcinoma (CNE2) Cisplatin S 91
Ovarian carcinoma (2008) Paclitaxel O 92
Breast cancer Neoadjuvant chemotherapy O 93
Breast cancer (MDA-MB-231), lung Adriamycin, etoposide O,S 94
adenocarcinoma (A549), lung fibrosarcoma
(HT1080)

Sorcin expression is upregulated in hepatocellular carcinoma, with respect to adjacent non-tumor liver
tissues and to normal liver tissues. Sorcin expression correlates with hepatocellular carcinoma metastasis:
patients with high Sorcin expression have shorter survival and higher recurrence compared with patients
with low Sorcin expression. Sorcin increases proliferation, migration, and invasion in vitro in hepatocellular
carcinoma and colorectal cancer cell, and facilitates cancer growth, metastasization and EMT, via activation
2+
of ERK and/or PI3K/Akt signaling pathways [79,97] . Sorcin is also involved in the regulation of Ca -mediated
angiogenesis, via the VEGF/PI3K/Akt pathway in endometrial cells and plays a crucial role in preparing the
[98]
endometrium for implantation .
Sorcin induces the expression of ABCB1 via a cAMP response element (CRE), located between -716 and
-709 base pairs upstream the ABCB1 gene: Sorcin overexpression increases CRE-binding protein (CREB)
[72]
phosphorylation and its binding to the CRE site in the ABCB1 promoter induces ABCB1 expression .