MCM7 supports the stemness of bladder cancer stem-like cells by enhancing autophagic flux

Abstract

Summary: 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.

Keywords

• Biological sciences
• Stem cells research
• Systems biology
• Cancer