Lin Wenyu, Wang Chaoqun, Liu Guangping, Bi Chao, Wang Xian, Zhou Qiyin, Jin Hongchuan
Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou 310016, Zhejiang, China.
Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University Dongyang 322100, Zhejiang, China.
Am J Cancer Res. 2020 Oct 1;10(10):3106-3126. eCollection 2020.
Amino acid transporters mediate substrates across cellular membranes and their fine-tuned regulations are critical to cellular metabolism, growth, and death. As the functional component of system Xc-, which imports extracellular cystine with intracellular glutamate release at a ratio of 1:1, SLC7A11 has diverse functional roles in regulating many pathophysiological processes such as cellular redox homeostasis, ferroptosis, and drug resistance in cancer. Notably, accumulated evidence demonstrated that SLC7A11 is overexpressed in many types of cancers and is associated with patients' poor prognosis. As a result, SLC7A11 becomes a new potential target for cancer therapy. In this review, we first briefly introduce the structure and function of SLC7A11, then discuss its pathological role in cancer. We next summarize current available data of how SLC7A11 is subjected to fine regulations at multiple levels. We further describe the potential inhibitors of the SLC7A11 and their roles in human cancer cells. Finally, we propose novel insights for future perspectives on the modulation of SLC7A11, as well as possible targeted strategies for SLC7A11-based anti-cancer therapies.
氨基酸转运体介导底物跨细胞膜转运，其精细调控对细胞代谢、生长和死亡至关重要。作为系统Xc-的功能组成部分，SLC7A11以1:1的比例将细胞外胱氨酸转运入细胞内并释放细胞内谷氨酸，在调节许多病理生理过程中发挥着多种功能作用，如细胞氧化还原稳态、铁死亡和癌症耐药性。值得注意的是，越来越多的证据表明，SLC7A11在多种癌症中过度表达，并与患者的不良预后相关。因此，SLC7A11成为癌症治疗的一个新的潜在靶点。在这篇综述中，我们首先简要介绍SLC7A11的结构和功能，然后讨论其在癌症中的病理作用。接下来，我们总结目前关于SLC7A11如何在多个水平上受到精细调控的现有数据。我们进一步描述SLC7A11的潜在抑制剂及其在人类癌细胞中的作用。最后，我们提出了关于SLC7A11调控的未来展望的新见解，以及基于SLC7A11的抗癌治疗的可能靶向策略。
