The nuclear transporter importin-11 regulates the Wnt/β-catenin pathway and acts as a tumor promoter in glioma.

Abstract

Karyopherins mediate the macromolecular transport between the cytoplasm and the nucleus and participate in cancer progression. However, the role and mechanism of importin-11 (IPO11), a member of the karyopherin family, in glioma progression remain undefined. Effects of IPO11 on glioma progression were detected using CCK-8, colony formation assay, flow cytometry analysis, caspase-3 activity assay, and Transwell invasion assay. Western blot analysis was used to detect the expression of active caspase-3, active caspase-7, active caspase-9, N-cadherin, Vimentin, E-cadherin, β-catenin, and c-Myc. The activity of Wnt/β-catenin pathway was evaluated by the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor reporter assay. Results showed that IPO11 knockdown inhibited proliferation and reduced colony number in glioma cells. IPO11 silencing promoted the apoptotic rate, increased expression levels of active caspase-3, caspase-7, and caspase-9, and enhanced caspase-3 activity. Moreover, IPO11 silencing inhibited glioma cell invasion by suppressing epithelial-to-mesenchymal transition (EMT). Mechanistically, IPO11 knockdown inactivated the Wnt/β-catenin pathway. β-Catenin overexpression abolished the effects of IPO11 silencing on the proliferation, apoptosis, and invasion in glioma cells. Furthermore, IPO11 silencing blocked the malignant phenotypes and repressed the Wnt/β-catenin pathway in vivo. In conclusion, IPO11 knockdown suppressed the malignant phenotypes of glioma cells by inactivating the Wnt/β-catenin pathway.

• Authors: Hongzao Ni, Daofei Ji, Jing Li, Zongren Zhao, Jiandong Zuo
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 176 Pg. 145-156 (Apr 15 2021) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 33571591 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• CTNNB1 protein, human
• Carcinogens
• IPO11 protein, human
• beta Catenin
• beta Karyopherins

Topics

• Animals
• Apoptosis (genetics, physiology)
• Brain Neoplasms (genetics, metabolism, pathology)
• Carcinogens (antagonists & inhibitors, metabolism)
• Cell Line, Tumor
• Cell Proliferation (genetics, physiology)
• Female
• Gene Knockdown Techniques
• Glioma (genetics, metabolism, pathology)
• Heterografts
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness (genetics, pathology, physiopathology)
• Phenotype
• Transcriptome
• Up-Regulation
• Wnt Signaling Pathway
• beta Catenin (genetics, metabolism)
• beta Karyopherins (antagonists & inhibitors, genetics, metabolism)