The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling
Abstract Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein that plays critical roles in the regulation of microtubule dynamics and maintenance of the Golgi structure. However, its biological role in human cancer remains largely unknown. In this study, we sho...
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07621-y |
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| _version_ | 1823861703673118720 |
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| author | Yangyang Fu Shishun Huang Rulu Pan Xingan Chen Ting Liu Rongzhe Zhang Fangsheng Zhu Qiwei Fang Liyue Wu Juji Dai Ouchen Wang Liting Lu Xiduan Wei Liangxing Wang Xincheng Lu |
| author_facet | Yangyang Fu Shishun Huang Rulu Pan Xingan Chen Ting Liu Rongzhe Zhang Fangsheng Zhu Qiwei Fang Liyue Wu Juji Dai Ouchen Wang Liting Lu Xiduan Wei Liangxing Wang Xincheng Lu |
| author_sort | Yangyang Fu |
| collection | DOAJ |
| description | Abstract Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein that plays critical roles in the regulation of microtubule dynamics and maintenance of the Golgi structure. However, its biological role in human cancer remains largely unknown. In this study, we showed that PDE4DIP is overexpressed in human non-small cell lung cancer (NSCLC) tissues and that upregulated PDE4DIP expression is associated with poor prognosis in patients with lung cancer. We demonstrated that PDE4DIP knockdown inhibits NSCLC cell proliferation in vitro and tumorigenicity in vivo. We further demonstrated that PDE4DIP knockdown triggers apoptosis and cell cycle arrest in NSCLC cells by activating the Protein kinase A (PKA) /CREB signalling pathway. PDE4DIP coordinates with A-kinase anchoring proteins 9 (AKAP9) to enhance the Golgi localization and stability of PKA RIIα. Depletion of PDE4DIP mislocalizes PKA RIIα from the Golgi and leads to its degradation, thereby compromising its negative regulatory effect on PKA signalling. Overall, our findings provide novel insights into the roles of the PDE4DIP-AKAP9 complex in regulating PKA signalling and NSCLC growth and highlight PDE4DIP as a promising therapeutic target for NSCLC. |
| format | Article |
| id | doaj-art-24679cdaf445492ebab94f3ba05d21b6 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-24679cdaf445492ebab94f3ba05d21b62025-02-09T12:50:32ZengNature PortfolioCommunications Biology2399-36422025-02-018111310.1038/s42003-025-07621-yThe PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signallingYangyang Fu0Shishun Huang1Rulu Pan2Xingan Chen3Ting Liu4Rongzhe Zhang5Fangsheng Zhu6Qiwei Fang7Liyue Wu8Juji Dai9Ouchen Wang10Liting Lu11Xiduan Wei12Liangxing Wang13Xincheng Lu14Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversityDepartment of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversityDivision of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical UniversitySchool of Basic Medical Sciences, Wenzhou Medical UniversityAbstract Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein that plays critical roles in the regulation of microtubule dynamics and maintenance of the Golgi structure. However, its biological role in human cancer remains largely unknown. In this study, we showed that PDE4DIP is overexpressed in human non-small cell lung cancer (NSCLC) tissues and that upregulated PDE4DIP expression is associated with poor prognosis in patients with lung cancer. We demonstrated that PDE4DIP knockdown inhibits NSCLC cell proliferation in vitro and tumorigenicity in vivo. We further demonstrated that PDE4DIP knockdown triggers apoptosis and cell cycle arrest in NSCLC cells by activating the Protein kinase A (PKA) /CREB signalling pathway. PDE4DIP coordinates with A-kinase anchoring proteins 9 (AKAP9) to enhance the Golgi localization and stability of PKA RIIα. Depletion of PDE4DIP mislocalizes PKA RIIα from the Golgi and leads to its degradation, thereby compromising its negative regulatory effect on PKA signalling. Overall, our findings provide novel insights into the roles of the PDE4DIP-AKAP9 complex in regulating PKA signalling and NSCLC growth and highlight PDE4DIP as a promising therapeutic target for NSCLC.https://doi.org/10.1038/s42003-025-07621-y |
| spellingShingle | Yangyang Fu Shishun Huang Rulu Pan Xingan Chen Ting Liu Rongzhe Zhang Fangsheng Zhu Qiwei Fang Liyue Wu Juji Dai Ouchen Wang Liting Lu Xiduan Wei Liangxing Wang Xincheng Lu The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling Communications Biology |
| title | The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling |
| title_full | The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling |
| title_fullStr | The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling |
| title_full_unstemmed | The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling |
| title_short | The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling |
| title_sort | pde4dip akap9 axis promotes lung cancer growth through modulation of pka signalling |
| url | https://doi.org/10.1038/s42003-025-07621-y |
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