2024.04.18
PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells
A research group led by Associate Professor Takashi Ohama at Yamaguchi University has elucidated a novel mechanism by which cancer stem cells maintain their stem cell properties. Cancer recurrence and metastasis are attributed to treatment-resistant cancer stem cells, making therapies targeting them highly anticipated.
The tumor suppressor PP2A is suppressed in cancer cells by inhibitory proteins such as SET, enhancing the stem cell-like properties of these cells. However, since this mechanism does not apply to some cancer cell lines, the research group attempted to elucidate a new stem cell maintenance mechanism using HOS cells.
They discovered that SET suppresses PP2A activity, thereby activating Akt. This activated Akt enhances cancer cell stemness by activating the mTORC1/p70S6K signaling pathway and stabilizing the Bmi-1 protein.
These findings were published in the Journal of Biological Chemistry and are expected to contribute to the development of novel therapies targeting cancer stem cells.
- Division of Translational Research for One Medicine
- Takashi Ohama（Basic Veterinary Science）
- Paper Title：PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells
- Authors：Naoki Kohyanagi, Nao Kitamura, Shunta Ikeda, Shusaku Shibutani, Koichi Sato, Takashi Ohama
- Journal:：Journal of Biological Chemistry
- Publication Date: December 22, 2023 (Online Publication)
- DOI：https://doi.org/10.1016/j.jbc.2023.105584
- ＜Research Inquiries＞
- Yamaguchi University,
Takashi Ohama (Basic Veterinary Science) - E-mail: t.ohama@yamaguchi-u.ac.jp
- ＜Public Relations＞
- Yamaguchi University Research Institute for Cell Design Medical Science (Life Science Support Section, Academic Research Division)
- Tel: 0836-85-3065
- E-mail: sh088@yamaguchi-u.ac.jp