Therapeutic strategies for cancer stem cells by regulating cellular differentiation based on actin dynamics

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18426
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Keio University
• Principal Investigator: NOBUSUE HIROYUKI 慶應義塾大学, 医学部(信濃町), 特任助教 (90525685)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 分化制御 / アクチン細胞骨格 / 骨肉腫

Outline of Final Research Achievements

Osteosarcoma-initiating (OSi) cells are composed of two distinct types: AO cells, which have characteristics similar to mesenchymal stem cells, and AX cells, which have those similar to osteo-chondro progenitor cell and highly tumorigenic. We found that AO cells are highly resistant to chemotherapeutic agents, such as adriamycin and cisplatin. Treatment with the ROCK inhibitor fasudil alone induced remodeling of the actin cytoskeleton and inactivation of the transcriptional coactivator MKL1, resulting in the terminal adipocyte differentiation of chemoresistant stem-like AO cells. Furthermore, fasudil significantly suppressed in vitro growth and in vivo tumorigenesis of AO cells. Our findings suggest that induction of trans-differentiation by regulating actin cytoskeleton dynamics is a potential approach for chemoresistant stem-like OS cells.

Free Research Field

腫瘍生物学