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ABC 亚家族 A 转运蛋白:癌症中具有初步潜力的多面手。

The ABC subfamily A transporters: Multifaceted players with incipient potentialities in cancer.

机构信息

CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, 40136, Italy.

CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, 40136, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, 40126, Italy.

出版信息

Semin Cancer Biol. 2020 Feb;60:57-71. doi: 10.1016/j.semcancer.2019.10.004. Epub 2019 Oct 9.

Abstract

Overexpression of ATP-binding cassette (ABC) transporters is a cause of drug resistance in a plethora of tumors. More recent evidence indicates additional contribution of these transporters to other processes, such as tumor cell dissemination and metastasis, thereby extending their possible roles in tumor progression. While the role of some ABC transporters, such as ABCB1, ABCC1 and ABCG2, in multidrug resistance is well documented, the mechanisms by which ABC transporters affect the proliferation, differentiation, migration and invasion of cancer cells are still poorly defined and are frequently controversial. This review, summarizes recent advances that highlight the role of subfamily A members in cancer. Emerging evidence highlights the potential value of ABCA members as biomarkers of risk and response in different tumors, but information is disperse and very little is known about their possible mechanisms of action. The only clear evidence is that ABCA members are involved in lipid metabolism and homeostasis. In particular, the relationship between ABCA1 and cholesterol is becoming evident in different fields of biology, including cancer. In parallel, emerging findings indicate that cholesterol, the main component of cell membranes, can influence many physiological and pathological processes, including cell migration, cancer progression and metastasis. This review aims to link the dispersed knowledge regarding the relationship of ABCA members with lipid metabolism and cancer in an effort to stimulate and guide readers to areas that the writers consider to have significant impact and relevant potentialities.

摘要

多药耐药性相关的 ABC 转运蛋白的过度表达是众多肿瘤产生耐药性的原因之一。最近的证据表明,这些转运蛋白还可能通过其他途径促进肿瘤细胞的扩散和转移,从而扩大了它们在肿瘤进展中的潜在作用。虽然一些 ABC 转运蛋白(如 ABCB1、ABCC1 和 ABCG2)在多药耐药性中的作用已得到充分证实,但 ABC 转运蛋白影响癌细胞增殖、分化、迁移和侵袭的机制仍未得到明确界定,并且经常存在争议。

本综述总结了近期的研究进展,强调了 ABCA 亚家族成员在癌症中的作用。新出现的证据强调了 ABCA 成员作为不同肿瘤风险和反应的生物标志物的潜在价值,但信息分散,对其可能的作用机制知之甚少。唯一明确的证据是 ABCA 成员参与了脂质代谢和稳态。特别是,ABCA1 与胆固醇之间的关系在包括癌症在内的不同生物学领域变得明显。

与此同时,新出现的发现表明,细胞膜的主要成分胆固醇可以影响许多生理和病理过程,包括细胞迁移、癌症进展和转移。本综述旨在将有关 ABCA 成员与脂质代谢和癌症关系的分散知识联系起来,以激发和引导读者关注作者认为具有重大影响和潜在可能性的领域。

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