Hydroxyl-HIF2-alpha is potential therapeutic target for renal cell carcinomas.
Dormant cancer cells are deprivation-resistant, and cause a number of problems for therapeutic approaches for cancers. Renal cell carcinomas (RCCs) include deprivation-resistant cells that are resistant to various treatments. In this study, the specific characteristics of deprivation-resistant cells were transcriptionally identified by next generation sequencing. The hypoxia-inducible factors (HIF) transcription factor network was significantly enhanced in deprivation-resistant RCCs compared to the sensitive RCCs. Deprivation-resistant RCCs, that had lost Von Hippel-Lindau tumor suppressor expression, expressed hydroxyl-HIF2-alpha in the nucleus, but not sensitive-RCCs. Hydroxyl-HIF-alpha was also expressed in nuclei of RCC tissue samples. Knockdown for HIF2-alpha, but not HIF1-alpha, induced cell death related to a reduction in HIF-related gene expression in deprivation-resistant RCC cells. Chetomin, a nuclear HIF-inhibitor, induced marked level of cytotoxicity in deprivation-resistant cells, similar to the knockdown of HIF2-alpha. Therefore, hydroxyl-HIF2-alpha might be a potential therapeutic target for RCCs.
Central Research Laboratory, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Takahiro
T
Isono
Department of Clinical Laboratory Medicine, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Tokuhiro
T
Chano
Department of Urology, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Tetsuya
T
Yoshida
Department of Urology, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Susumu
S
Kageyama
Department of Urology, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Akihiro
A
Kawauchi
Central Research Laboratory, Shiga University of Medical Science Otsu, Shiga 520-2192, Japan.
Masafumi
M
Suzaki
Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Tokyo 135-8550, Japan.
Takeshi
T
Yuasa
HIF2-alpha; Hypoxia-inducible factors (HIF); POU5F1; Von Hippel-Lindau (VHL); chetomin; deprivation; global transcriptome; hydroxyl-HIF-alpha; next generation sequencer (NGS); renal cell carcinoma (RCC)