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索辛在癌症发展和化疗耐药中的作用

Sorcin in Cancer Development and Chemotherapeutic Drug Resistance.

作者信息

Exertier Cécile, Antonelli Lorenzo, Fiorillo Annarita, Bernardini Roberta, Colotti Beatrice, Ilari Andrea, Colotti Gianni

机构信息

Institute of Molecular Biology and Pathology, Italian National Research Council (IBPM-CNR), c/o Department Biochemical Sciences, Sapienza University of Rome, Ed. CU027, P.le A.Moro 5, 00185 Rome, Italy.

Department Biochemical Sciences, Sapienza University of Rome, Ed. CU027, P.le A.Moro 5, 00185 Rome, Italy.

出版信息

Cancers (Basel). 2024 Aug 9;16(16):2810. doi: 10.3390/cancers16162810.

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.

摘要

可溶性耐药相关钙结合蛋白(Sorcin)因其在多药耐药细胞中与ABCB1共同扩增而得名。最初认为这种共同扩增是偶然结果,但最近的研究表明,Sorcin作为一种癌蛋白发挥着更积极的作用,对多药耐药(MDR)有显著影响。Sorcin是一种高表达的钙结合蛋白,在人类肿瘤和多药耐药癌症中常过度产生,是一种有前景的新型MDR标志物。在肿瘤中,Sorcin水平与患者对化疗的反应和总体预后呈负相关。与亲代细胞系相比,多药耐药细胞系始终表现出更高的Sorcin表达。此外,通过基因转染过表达Sorcin可增强多种癌症细胞系对各种化疗药物的耐药性。相反,沉默Sorcin表达可逆转许多细胞系中的耐药性。Sorcin参与多种MDR机制,包括药物外排、药物隔离、细胞死亡抑制、基因扩增、上皮-间质转化、血管生成和转移。本综述重点关注Sorcin的结构和功能、Sorcin在癌症和耐药性中的作用以及针对Sorcin的靶向方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2d/11352664/dea82b626124/cancers-16-02810-g001.jpg

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