TY - JOUR
T1 - The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis
AU - Wang, Zuli
AU - Ouyang, Lianlian
AU - Liu, Na
AU - Li, Tiansheng
AU - Yan, Bokang
AU - Mao, Chao
AU - Xiao, Desheng
AU - Gan, Boyi
AU - Liu, Shuang
AU - Tao, Yongguang
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.
AB - Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.
UR - http://www.scopus.com/inward/record.url?scp=85166647898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85166647898&partnerID=8YFLogxK
U2 - 10.1038/s41388-023-02744-0
DO - 10.1038/s41388-023-02744-0
M3 - Article
C2 - 37537342
AN - SCOPUS:85166647898
SN - 0950-9232
VL - 42
SP - 2688
EP - 2700
JO - Oncogene
JF - Oncogene
IS - 36
ER -