Imbalance of pH homeostasis: a trigger for tumorigenesis?

Hiroshi Harada

Research Site	Kyoto University
	Radiation Biology Center
	Professor

Content

Maintaining genomic stability in tissue stem cells is critical for proper development of our body. This project aims to reveal functional roles of pH homeostasis in it and also to elucidate molecular mechanisms underlying how disordered pH homeostasis triggers neoplasmic cell transformation.

Publication

1. Kobayashi M, Morinibu A, Koyasu S, Goto Y, Hiraoka M, *Harada H. A circadian clock gene, PER2, activates HIF-1 as an effector molecule for recruitment of HIF-1alpha to promoter regions of its downstream genes. FEBS J. 284: 3804-3816. 2017.
   （*Corresponding author）
2. Nakashima R, Goto Y, Koyasu S, Kobayashi M, Morinibu A, Yoshimura M, Hiraoka　M, Hammond EM, Harada H. UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization. Scientific Reports. 7:6879. 2017.
3. Yeom CJ, Zeng L, Goto Y, Morinibu A, Zhu Y, Shinomiya K, Kobayashi M, Itasaka S, Yoshimura M, HurCG, Kakeya H, Hammond EM, Hiraoka M, *Harada H. LY6E: a conductor of malignant tumor growth through modulation of the PTEN/PI3K/Akt/HIF-1 axis. Oncotarget. 11670. 2016. （*Corresponding author）
4. Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T, Hirota K, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hammond EM, Hiraoka M, *Harada H. Aberrant IDH3alpha expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis. Oncogene. 34:4758-4766. 2015.
   （*Corresponding author）
5. Goto Y, Zeng L, Yeom CJ, Zhu Y, Morinibu A, Shinomiya K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Torii M, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, *Harada H. UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α. Nature Communications. 6: 6153. 2015. （*Corresponding author）