Abstract
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.
Highlights
Pokemon, an erythroid myeloid ontogenic factor, is a member of the POK (POZ and Krüppel) family of transcriptional repressors [1]
We examined the expression of the Pokemon protein in three human hepatoma and two non-malignant liver cell lines
The results showed that stably expressed Pokemon impaired detachment-induced Bim accumulation and anoikis and that this effect was reversed by small interfering RNAs (siRNA) knockdown of Pokemon (Figure 4c)
Summary
An erythroid myeloid ontogenic factor, is a member of the POK (POZ and Krüppel) family of transcriptional repressors [1]. Pokemon prevents apoptosis via suppression of p53 and Bim to promote cell survival with a tendency towards transformation. Pokemon represses p21 and Rb expression to promote cell cycle progression. Pokemon has many functions in cancer cells that promote cell survival and cell cycle progression. These functions may be essential for embryonic development. The abrogation of Pokemon expression leads to lethal anemia in mouse embryos due to apoptosis of late-stage erythroblasts. This programmed cell death is mediated by upregulation of the pro-apoptotic factor, Bim, in Pokemon-null cells.
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