文章基本信息

标题：MCM7 supports the stemness of bladder cancer stem-like cells by enhancing autophagic flux
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作者：Lijun Mo ; Bijia Su ; Lili Xu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-22
DOI：10.1016/j.isci.2022.105029
语种：English
出版社：Elsevier
摘要：SummaryAutophagy plays critical roles in the pluripotent stemness of cancer stem cells (CSCs). However, how CSCs maintain the elevated autophagy to support stemness remains elusive. Here, we demonstrate that bladder cancer stem-like cells (BCSLCs) are at slow-cycling state with enhanced autophagy and mitophagy. In these slow-cycling BCSLCs, the DNA replication initiator MCM7 is required for autophagy and stemness. MCM7 knockdown inhibits autophagic flux and reduces the stemness of BCSLCs. MCM7 can facilitate autolysosome formation through binding with dynein to promote autophagic flux. The enhanced autophagy/mitophagy helps BCSLCs to maintain mitochondrial respiration, thus inhibiting AMPK activation. AMPK activation can trigger switch from autophagy to apoptosis, through increasing BCL2/BECLIN1 interaction and inducing P53 accumulation. In summary, we find that MCM7 can promote autophagic flux to support.Graphical abstractDisplay OmittedHighlights•Enhancement of autophagy and mitophagy in bladder cancer stem-like cells (BCSLCs)•The autophagy/mitophagy sustains BCSLCs stemness•MCM7 facilitates autophagic flux to support BCSLCs stemnessBiological sciences; Stem cells research; Systems biology; Cancer.