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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 173

Figure 6. The ABCB1 amplicon is formed by the genes SRI, ADAM22, DBF4, SLC25A40, RUNDC3B (RPIP9), ABCB1, ABCB4, CROT,
TP53TG1 lncRNA, TMEM243 (MGC4175) and DMTF1 (DMP1)

with the efflux pumps ABCB1 and ABCB4 (MDR3): DBF4 and Sorcin are both important markers of
poor prognosis and drivers of MDR in several types of cancers, acting on different (although partially
overlapping) mechanisms with respect to ABCB1 .
[137]
In lung cancer cells with acquired paclitaxel resistance, the 7.q21.12 region is amplified, but ABCB1
expression is increased up to 1000-fold, showing a discrepancy between expression level and gene copy
number . A regional activation on chromosome 7q21.11-13, of about 22 co-expressed genes over an area
[133]
of 8 Mb, was identified in taxane-induced MD-resistant ovarian tumor cells; the amplified region (with
increase in genes copy number) included ABCB1, MGC4175 (TMEM243), DMTF1, CROT, ABCB1, ABCB4,
ADAM22, RUNDC3B, DBF4 and SRI . A gene copy number gain on chromosome 7q21.12, including the
[138]
genes ABCB1, ABCB4, SRI, DMTF1, SLC25A40 and CROT, was observed in taxane-resistant breast tumor
[129]
cell lines . On the other hand, MD-resistant ovarian tumor cells containing a translocation generating
fused ABCB1 and SLC25A40 genes, determining the overexpression of ABCB1, were found only in MD-
resistant cancers, while no evidence of this event occurs in drug-sensitive cancer cells . Deletions in
[131]
the ABCB1 genes locus in breast cancer patients determine a 2-8-fold decreased expression of these MDR
locus-related genes; cancer patients harboring these deletions display a better response to neoadjuvant
chemotherapy .
[130]
In addition to genomic rearrangements and presence of high copy, other mechanisms may contribute to
increased gene expression, such as transcriptional upregulation, mRNA stabilization, post-transcriptional
regulation and epigenetic modifications. Non-coding RNAs, such as miRNAs and long non-coding RNAs,
can possibly exert post-transcriptionally regulate oncogene functions on cancer cells, resulting in metastatic
or drug-resistant phenotypes: the long non-coding RNA TP53TG1, present in the chromosomal region
7.q21.12, is down-regulated in A549 cisplatin-resistant lung cancer cells ; miR-1, specifically targeting
[139]
Sorcin , is frequently downregulated in various types of cancer, such as lung cancer, colon cancer,
[36]
genitourinary cancer, head and neck tumor, thyroid cancer and sarcoma; low miR-1 levels have been shown
to be associated with chemosensitivity [140,141] .

CONCLUSION
Sorcin has an important role as a modulator of cellular calcium homeostasis, acting on Ca channels,
2+
exchangers and pumps, thereby regulating ER and mitochondrial Ca levels, reducing ER stress and
2+
mitochondrial dysfunction, and protecting the cell from apoptosis.

Sorcin is highly expressed in the heart and in the brain, it is overexpressed in cancers and other
pathological conditions, and plays important roles in the onset of cancer, cardiac diseases and possibly
neurodegenerative diseases.