4:45 PM - 5:00 PM
[US7-04] Metabolic properties and maintenance of stemness in cancer stem cells
Keywords:がん幹細胞、エネルギー代謝、メタボローム
Accumulating evidence suggests that cancer stem cells (CSCs) play important roles in cancer development, metastasis, recurrence and drug resistance. Understanding their properties and regulatory mechanisms is desirable for the development of effective anti-cancer drugs. We have found that stem cells are maintained by the chromosome passenger complex (CPC). Knockdown or compound inhibition of CPC components reduced the expression of stem cell markers, such as OCT4 and NANOG, and induced the expression of various differentiation markers. The expression of MYC protein, a master regulator of central metabolism, was upregulated during the differentiation. Combined with the alterations in the balance of glucose/glutamine dependency, MYC protein may remodel energy metabolism and enhance glycolytic drive. This raises the possibility that the CPC-MYC axis may serve as a metabolic checkpoint for stem cell maintenance. Moreover, CPC inhibition in a cancer stem cell model significantly enhanced the efficacy of MYC inhibitors, raising the possibility of a new therapeutic avenue to enhance drug sensitivity. Our findings reveal a novel regulatory mechanism for stemness maintenance and pave the way for effective drug combination therapies that coordinate differentiation induction and anti-cancer drugs.