MCM7 supports the sternness of bladder cancer stern-like cells by enhancing autophagic flux

作者：Mo, Lijun; Su, Bijia; Xu, Lili; Hu, Zhiming; Li, Hongwei; Du, Hongyan; Li, Jinlong^*

来源：iScience, 2022, 25(9): 105029.

DOI：10.1016/j.isci.2022.105029

• AMPK
• PROTEIN
• PHOSPHORYLATION
• CHEMOTHERAPY
• DNA

Autophagy 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.

• 单位
  南方医科大学