癌症研究
基因沉默
乳腺癌
癌症
癌细胞
胱硫醚β合酶
生物
肿瘤进展
半胱氨酸
生物化学
基因
酶
遗传学
作者
Wenwen Xue,Yuan Yin,Yongzhong Yao,Lin Zhou,Ying Huang,Yixuan Wang,Zhixiu Chen,Liwei Wang,Xinran Li,Xiaoning Wang,Ronghui Du,Yan Shen,Qiang Xu
标识
DOI:10.1016/j.redox.2024.103034
摘要
Cytokine-like protein 1 (CYTL1) expression is deliberately downregulated during the progression of multiple types of cancers, especially breast cancer. However, the metabolic characteristics of cancer progression remain unclear. Here, we uncovered a risk of breast cancer cells harboring low CYTL1 expression, which is metabolically controlled during malignant progression. We performed metabolism comparison and revealed that breast cancer cells with low CYTL1 expression have highly suppressed transsulfuration activity that is driven by cystathionine β-synthase (CBS) and contributes to de novo cysteine synthesis. Mechanistically, CYTL1 activated Nrf2 by promoting autophagic Keap1 degradation, and Nrf2 subsequently transactivated CBS expression. Due to the lack of cellular cysteine synthesis, breast cancer cells with low CYTL1 expression showed hypersensitivity to system xc− blockade-induced ferroptosis in vitro and in vivo. Silencing CBS counteracted CYTL1-mediated ferroptosis resistance. Our results show the importance of exogeneous cysteine in breast cancer cells with low CYTL1 expression and highlight a potential metabolic vulnerability to target.
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