Li Sijia, Lu Zhenyao, Sun Runbin, Guo Suhan, Gao Fangfang, Cao Bei, Aa Jiye
China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing 210000, China.
Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Cancers (Basel). 2022 Jun 22;14(13):3059. doi: 10.3390/cancers14133059.
SLC7A11 controls the uptake of extracellular cystine in exchange for glutamate at a ratio of 1:1, and it is overexpressed in a variety of tumours. Accumulating evidence has shown that the expression of SLC7A11 is fine-tuned at multiple levels, and plays diverse functional and pharmacological roles in tumours, such as cellular redox homeostasis, cell growth and death, and cell metabolism. Many reports have suggested that the inhibition of SLC7A11 expression and activity is favourable for tumour therapy; thus, SLC7A11 is regarded as a potential therapeutic target. However, emerging evidence also suggests that on some occasions, the inhibition of SLC7A11 is beneficial to the survival of cancer cells, and confers the development of drug resistance. In this review, we first briefly introduce the biological properties of SLC7A11, including its structure and physiological functions, and further summarise its regulatory network and potential regulators. Then, focusing on its role in cancer, we describe the relationships of SLC7A11 with tumourigenesis, survival, proliferation, metastasis, and therapeutic resistance in more detail. Finally, since SLC7A11 has been linked to cancer through multiple approaches, we propose that its contribution and regulatory mechanism require further elucidation. Thus, more personalised therapeutic strategies should be adapted when targeting SLC7A11.
溶质载体家族7成员11（SLC7A11）以1:1的比例控制细胞外胱氨酸与谷氨酸的交换摄取，并且在多种肿瘤中过表达。越来越多的证据表明，SLC7A11的表达在多个水平上受到精细调控，并且在肿瘤中发挥多种功能和药理作用，如细胞氧化还原稳态、细胞生长与死亡以及细胞代谢。许多报道表明，抑制SLC7A11的表达和活性有利于肿瘤治疗；因此，SLC7A11被视为一个潜在的治疗靶点。然而，新出现的证据也表明，在某些情况下，抑制SLC7A11有利于癌细胞的存活，并导致耐药性的产生。在这篇综述中，我们首先简要介绍SLC7A11的生物学特性，包括其结构和生理功能，并进一步总结其调控网络和潜在的调控因子。然后，聚焦于其在癌症中的作用，我们更详细地描述SLC7A11与肿瘤发生、存活、增殖、转移和治疗耐药性之间的关系。最后，由于SLC7A11已通过多种途径与癌症相关联，我们提出其作用和调控机制需要进一步阐明。因此，在靶向SLC7A11时应采用更具个性化的治疗策略。
