<p>Sorcin: a novel potential target in therapies of cancers</p>

Abstract

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic diseases. Research proved that sorcin can be found to overexpress in cells of several cancers, particularly in the case of multidrug-resistant cancers. Additionally, the researchers proposed that the expression of sorcin was significantly associated with the foundation of multidrug resistance (MDR). All the findings mentioned above emphasized the importance of studying sorcin. This review mainly includes the following aspects: functions of sorcin, role in non-neoplastic and neoplastic diseases, and research related to drugs. To sum up, sorcin is a potential novel target to be studied to deal with MDR.

Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity

“…As mentioned above, sorcin is widely distributed in human tissues. Several studies propose its involvement in Ca 2+ homeostasis, cell cycle regulation and vesicle trafficking, diabetes, infertility and nervous system pathologies (reviewed in [ 40 ]), although most studies on sorcin are related to its overexpression in tumor cells [ 2 , 40 , 41 ] and to its regulatory role in excitation–contraction coupling in the heart through its interaction with several proteins, such as the SERCA pump [ 16 ], the ryanodine receptor intracellular Ca 2+ channel [ 15 , 42 ], the Na + -Ca 2+ exchanger [ 18 ] and L-type Ca 2+ channels [ 43 ]. Mass spectrometric and database analyses have shown that sorcin is highly expressed in the brain [ 44 , 45 , 46 ].…”

Editorial: The role of calcium and calcium binding proteins in cell physiology and disease

“…The review describes how these reporters could be used to pinpoint Ca 2+ sensitive processes in mitosis, such as when GCaMP6 tethered to actin, nucleated at centrosomes and detected Ca 2+ signals thought to play a role in orienting the mitotic spindle (Farina et al, 2016;Helassa et al, 2019;Lagos-Cabre et al, 2020). The authors also emphasise the importance of Ca 2+ binding proteins in mitosis, dysregulation of which may affect protein kinase activation (Lee et al, 2014;Zhou et al, 2019), altered gene expression and ultimately oncogenesis and the development of anti-cancer drugs which target Ca 2+ signalling components is a burgeoning field of therapeutics (Roderick and Cook, 2008;Monteith et al, 2017).…”

Mitosis, Focus on Calcium

“…In addition to calmodulin and CaBP7, a variety of other small calcium sensing proteins have been linked to mitosis progression. Sorcin, a small penta-EF hand calcium sensor, exhibits mitosis specific changes in cellular localisation (Lalioti et al, 2014) and is over-expressed in multiple human cancers (Zhou et al, 2019). It has been linked to the multidrug resistant phenotype of certain cancers and is therefore of significant interest as a clinically relevant target (Pomeroy et al, 2002;Tan et al, 2003;Yokota et al, 2006;Nagpal and Das, 2007;Zhou et al, 2019).…”

“…Sorcin, a small penta-EF hand calcium sensor, exhibits mitosis specific changes in cellular localisation (Lalioti et al, 2014) and is over-expressed in multiple human cancers (Zhou et al, 2019). It has been linked to the multidrug resistant phenotype of certain cancers and is therefore of significant interest as a clinically relevant target (Pomeroy et al, 2002;Tan et al, 2003;Yokota et al, 2006;Nagpal and Das, 2007;Zhou et al, 2019). Early in mitosis, sorcin-positive vesicles associate with the spindle and later, at cytokinesis, they are found in the cleavage furrow and at the midbody (Lalioti et al, 2014).…”