奥沙利铂
结直肠癌
转录因子
下调和上调
基因敲除
化学
内科学
基因沉默
癌症
癌症研究
医学
生物
生物化学
细胞凋亡
基因
作者
Haoran Jiang,Yuan Zeng,Xue Jiang,Xuni Xu,Lihao Zhao,Xiaoye Yuan,Jun Xu,Mengjing Zhao,Fang Wu,Gang Li
标识
DOI:10.1016/j.bbadis.2024.167210
摘要
Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.
科研通智能强力驱动
Strongly Powered by AbleSci AI