Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity
Pancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and...
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3885 |
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| author | Yichen Guo Yinan Jiang J. Bart Rose Ganji Purnachandra Nagaraju Renata Jaskula-Sztul Anita B. Hjelmeland Adam W. Beck Herbert Chen Bin Ren |
| author_facet | Yichen Guo Yinan Jiang J. Bart Rose Ganji Purnachandra Nagaraju Renata Jaskula-Sztul Anita B. Hjelmeland Adam W. Beck Herbert Chen Bin Ren |
| author_sort | Yichen Guo |
| collection | DOAJ |
| description | Pancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study, we demonstrate that CSCs in human pNETs co-express protein kinase PKD1 and CD44. We further identify PKD1 signaling as a critical pathway in the control of CSC maintenance in pNET cells. PKD1 signaling regulates the expression of a CSC- and EMT-related gene signature and promotes CSC self-renewal, likely leading to the preservation of a subpopulation of CSCs at an intermediate EMT state. This suggests that the PKD1 signaling pathway may be required for the development of a unique CSC phenotype with plasticity and partial EMT. Given that the signaling networks connected with CSC maintenance and EMT are complex, and extend through multiple levels of regulation, this study provides insight into signaling regulation of CSC plasticity and partial EMT in determining the fate of CSCs. Inhibition of the PKD1 pathway may facilitate the elimination of specific CSC subsets, thereby curbing tumor progression and metastasis. |
| first_indexed | 2024-03-09T17:50:56Z |
| format | Article |
| id | doaj.art-ff6f6e403cb140bfb558440ffe4a02a2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:56Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ff6f6e403cb140bfb558440ffe4a02a22023-11-24T10:45:24ZengMDPI AGCells2073-44092022-12-011123388510.3390/cells11233885Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal PlasticityYichen Guo0Yinan Jiang1J. Bart Rose2Ganji Purnachandra Nagaraju3Renata Jaskula-Sztul4Anita B. Hjelmeland5Adam W. Beck6Herbert Chen7Bin Ren8Department of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Medicine, Division of Hematology and Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USAO’Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Surgery, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USAPancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study, we demonstrate that CSCs in human pNETs co-express protein kinase PKD1 and CD44. We further identify PKD1 signaling as a critical pathway in the control of CSC maintenance in pNET cells. PKD1 signaling regulates the expression of a CSC- and EMT-related gene signature and promotes CSC self-renewal, likely leading to the preservation of a subpopulation of CSCs at an intermediate EMT state. This suggests that the PKD1 signaling pathway may be required for the development of a unique CSC phenotype with plasticity and partial EMT. Given that the signaling networks connected with CSC maintenance and EMT are complex, and extend through multiple levels of regulation, this study provides insight into signaling regulation of CSC plasticity and partial EMT in determining the fate of CSCs. Inhibition of the PKD1 pathway may facilitate the elimination of specific CSC subsets, thereby curbing tumor progression and metastasis.https://www.mdpi.com/2073-4409/11/23/3885cancer stem cellsCD36E-cadherinepithelial to mesenchymal transition (EMT)lysophosphatidic acid (LPA)pancreatic neuroendocrine tumors |
| spellingShingle | Yichen Guo Yinan Jiang J. Bart Rose Ganji Purnachandra Nagaraju Renata Jaskula-Sztul Anita B. Hjelmeland Adam W. Beck Herbert Chen Bin Ren Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity Cells cancer stem cells CD36 E-cadherin epithelial to mesenchymal transition (EMT) lysophosphatidic acid (LPA) pancreatic neuroendocrine tumors |
| title | Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity |
| title_full | Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity |
| title_fullStr | Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity |
| title_full_unstemmed | Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity |
| title_short | Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity |
| title_sort | protein kinase d1 signaling in cancer stem cells with epithelial mesenchymal plasticity |
| topic | cancer stem cells CD36 E-cadherin epithelial to mesenchymal transition (EMT) lysophosphatidic acid (LPA) pancreatic neuroendocrine tumors |
| url | https://www.mdpi.com/2073-4409/11/23/3885 |
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