Sorcin in Cancer Development and Chemotherapeutic Drug Resistance

Abstract

SOluble Resistance-related Calcium-binding proteIN (sorcin) earned its name due to its co-amplification with ABCB1 in multidrug-resistant cells. Initially thought to be an accidental consequence of this co-amplification, recent research indicates that sorcin plays a more active role as an oncoprotein, significantly impacting multidrug resistance (MDR). Sorcin is a highly expressed calcium-binding protein, often overproduced in human tumors and multidrug-resistant cancers, and is a promising novel MDR marker. In tumors, sorcin levels inversely correlate with both patient response to chemotherapy and overall prognosis. Multidrug-resistant cell lines consistently exhibit higher sorcin expression compared to their parental counterparts. Furthermore, sorcin overexpression via gene transfection enhances drug resistance to various chemotherapeutic drugs across numerous cancer lines. Conversely, silencing sorcin expression reverses drug resistance in many cell lines. Sorcin participates in several mechanisms of MDR, including drug efflux, drug sequestering, cell death inhibition, gene amplification, epithelial-to-mesenchymal transition, angiogenesis, and metastasis. The present review focuses on the structure and function of sorcin, on sorcin’s role in cancer and drug resistance, and on the approaches aimed at targeting sorcin.