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索辛,一种参与癌细胞多药耐药机制的钙结合蛋白。

Sorcin, a calcium binding protein involved in the multidrug resistance mechanisms in cancer cells.

作者信息

Colotti Gianni, Poser Elena, Fiorillo Annarita, Genovese Ilaria, Chiarini Valerio, Ilari Andrea

机构信息

Institute of Biology, Molecular Medicine and Nanobiotechnology, Consiglio Nazionale delle Ricerche, P.le A Moro 5, Rome 00185, Italy.

Department Biochemical Sciences "A. Rossi Fanelli", University Sapienza, P.le A. Moro 5, Rome 00185, Italy.

出版信息

Molecules. 2014 Sep 5;19(9):13976-89. doi: 10.3390/molecules190913976.

Abstract

Sorcin is a penta-EF hand calcium binding protein, which participates in the regulation of calcium homeostasis in cells. Sorcin regulates calcium channels and exchangers located at the plasma membrane and at the endo/sarcoplasmic reticulum (ER/SR), and allows high levels of calcium in the ER to be maintained, preventing ER stress and possibly, the unfolded protein response. Sorcin is highly expressed in the heart and in the brain, and overexpressed in many cancer cells. Sorcin gene is in the same amplicon as other genes involved in the resistance to chemotherapeutics in cancer cells (multi-drug resistance, MDR) such as ABCB4 and ABCB1; its overexpression results in increased drug resistance to a number of chemotherapeutic agents, and inhibition of sorcin expression by sorcin-targeting RNA interference leads to reversal of drug resistance. Sorcin is increasingly considered a useful marker of MDR and may represent a therapeutic target for reversing tumor multidrug resistance.

摘要

索辛是一种具有五个EF手型结构域的钙结合蛋白,参与细胞内钙稳态的调节。索辛调节位于质膜以及内质网/肌浆网(ER/SR)上的钙通道和交换体,使内质网中维持高水平的钙,防止内质网应激以及可能的未折叠蛋白反应。索辛在心脏和大脑中高表达,在许多癌细胞中过表达。索辛基因与癌细胞中其他参与化疗耐药性(多药耐药,MDR)的基因如ABCB4和ABCB1位于同一扩增子中;其过表达导致对多种化疗药物的耐药性增加,而通过靶向索辛的RNA干扰抑制索辛表达可导致耐药性逆转。索辛越来越被认为是多药耐药的一个有用标志物,可能代表逆转肿瘤多药耐药性的一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01e/6271628/5c76dfe0db47/molecules-19-13976-g001.jpg

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