PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis
| Autor: | Feng Jin, Feng Li, Xin Zhao, Hongyan Zhang, Danni Li, Jiabin Li, Fuyi Han, Yao Xing, Yang Li, Yanshu Li, Bingtao Hu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Membrane permeability
Carcinogenesis Breast Neoplasms Mitochondrion medicine.disease_cause Applied Microbiology and Biotechnology Permeability AIF breast cancer Breast cancer Cell Line Tumor Drug Discovery medicine Humans cardiovascular diseases Phosphorylation Molecular Biology Ecology Evolution Behavior and Systematics Membrane Potential Mitochondrial Chemistry Kinase apoptosis Apoptosis Inducing Factor Cell Biology medicine.disease Gene Expression Regulation Neoplastic Protein Transport p21-Activated Kinases PAK5 Apoptosis Mitochondrial Membranes Cancer research biological phenomena cell phenomena and immunity Signal transduction Signal Transduction Research Paper Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.58102 |
| Popis: | Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. PAK5 inhibits the release of AIF from mitochondria in breast cancer cells by decreasing the mitochondria membrane permeability and increasing the membrane potential. Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation. Functionally, we demonstrate that PAK5-mediated AIF phosphorylation promotes the proliferation of breast cancer cells and accelerates the growth of breast cancer in vivo. Significantly, PAK5 and AIF expression in breast cancer are positively correlated with poor patient prognosis. PAK5 expression is negatively correlated with AIF nuclear translocation. These results suggest that PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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