PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis
© The author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
International journal of biological sciences - 17(2021), 5 vom: 20., Seite 1315-1327 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xing, Yao [VerfasserIn] |
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| Links: |
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| Themen: |
AIF |
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| Anmerkungen: |
Date Completed 24.03.2022 Date Revised 24.03.2022 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.7150/ijbs.58102 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32422513X |
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| 245 | 1 | 0 | |a PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis |
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| 500 | |a Date Revised 24.03.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AIF | |
| 650 | 4 | |a PAK5 | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a breast cancer | |
| 650 | 7 | |a Apoptosis Inducing Factor |2 NLM | |
| 650 | 7 | |a PAK5 protein, human |2 NLM | |
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| 650 | 7 | |a p21-Activated Kinases |2 NLM | |
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| 700 | 1 | |a Li, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Bingtao |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Fuyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanshu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Danni |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiabin |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Feng |e verfasserin |4 aut | |
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