Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth
Abstract The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47633-4 |
| _version_ | 1797453342985682944 |
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| author | Barani Govindarajan Diego Sbrissa Mark Pressprich Seongho Kim Arun K. Rishi Ulka Vaishampayan Michael L. Cher Sreenivasa R. Chinni |
| author_facet | Barani Govindarajan Diego Sbrissa Mark Pressprich Seongho Kim Arun K. Rishi Ulka Vaishampayan Michael L. Cher Sreenivasa R. Chinni |
| author_sort | Barani Govindarajan |
| collection | DOAJ |
| description | Abstract The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4–PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells. Inhibiting PI4KIIIα or TTC7 reduces plasma membrane PI4P production, cellular invasion, and bone tumor growth. Using metastatic biopsy sequencing, we found PI4KA expression in tumors correlated with overall survival and contributes to immunosuppressive bone tumor microenvironment through preferentially enriching non-activated and immunosuppressive macrophage populations. Altogether we have characterized the chemokine signaling axis through CXCR4–PI4KIIIα interaction contributing to the growth of prostate cancer bone metastasis. |
| first_indexed | 2024-03-09T15:21:27Z |
| format | Article |
| id | doaj.art-72f203e958aa4b8ca95a10b6d2a6edb9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:21:27Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-72f203e958aa4b8ca95a10b6d2a6edb92023-11-26T12:47:42ZengNature PortfolioScientific Reports2045-23222023-11-0113111310.1038/s41598-023-47633-4Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growthBarani Govindarajan0Diego Sbrissa1Mark Pressprich2Seongho Kim3Arun K. Rishi4Ulka Vaishampayan5Michael L. Cher6Sreenivasa R. Chinni7Department of Pathology, Wayne State University, School of MedicineDepartment of Urology, Wayne State University, School of MedicineDepartment of Urology, Wayne State University, School of MedicineDepartment of Oncology, Wayne State University, School of MedicineDepartment of Oncology, Wayne State University, School of MedicineDepartment of Oncology, University of MichiganDepartment of Pathology, Wayne State University, School of MedicineDepartment of Pathology, Wayne State University, School of MedicineAbstract The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4–PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells. Inhibiting PI4KIIIα or TTC7 reduces plasma membrane PI4P production, cellular invasion, and bone tumor growth. Using metastatic biopsy sequencing, we found PI4KA expression in tumors correlated with overall survival and contributes to immunosuppressive bone tumor microenvironment through preferentially enriching non-activated and immunosuppressive macrophage populations. Altogether we have characterized the chemokine signaling axis through CXCR4–PI4KIIIα interaction contributing to the growth of prostate cancer bone metastasis.https://doi.org/10.1038/s41598-023-47633-4 |
| spellingShingle | Barani Govindarajan Diego Sbrissa Mark Pressprich Seongho Kim Arun K. Rishi Ulka Vaishampayan Michael L. Cher Sreenivasa R. Chinni Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth Scientific Reports |
| title | Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth |
| title_full | Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth |
| title_fullStr | Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth |
| title_full_unstemmed | Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth |
| title_short | Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth |
| title_sort | adaptor proteins mediate cxcr4 and pi4ka crosstalk in prostate cancer cells and the significance of pi4ka in bone tumor growth |
| url | https://doi.org/10.1038/s41598-023-47633-4 |
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