Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer
DKK3 is a secreted protein, which belongs to a family of Wnt antagonists and acts as a potential tumor suppressor in gallbladder cancer. To further understand its tumor suppressor functions, we overexpressed DKK3 in 3 GBC cell lines. We have employed high-resolution mass spectrometry and tandem mass...
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/3/511 |
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| author | Kirti Gondkar Gajanan Sathe Neha Joshi Bipin Nair Akhilesh Pandey Prashant Kumar |
| author_facet | Kirti Gondkar Gajanan Sathe Neha Joshi Bipin Nair Akhilesh Pandey Prashant Kumar |
| author_sort | Kirti Gondkar |
| collection | DOAJ |
| description | DKK3 is a secreted protein, which belongs to a family of Wnt antagonists and acts as a potential tumor suppressor in gallbladder cancer. To further understand its tumor suppressor functions, we overexpressed DKK3 in 3 GBC cell lines. We have employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography to enrich phosphopeptides to check the downstream regulators. In this study, we reported for the first time the alteration in the phosphorylation of 14 kinases upon DKK3 overexpression. In addition, we observed DKK3 induced hyper phosphorylation of 2 phosphatases: PPP1R12A and PTPRA, which have not been reported previously. Canonical pathway analysis of altered molecules indicated differential enrichment of signaling cascades upon DKK3 overexpression in all the 3 cell lines. Protein kinase A signaling, Sirtuin signaling pathway, and Cell Cycle Control of Chromosomal Replication were observed to be differentially activated in the GBC cell lines. Our study revealed, DKK3 overexpression has differential effect based on the aggressive behavior of the cell lines. This study expands the understanding of DKK3-mediated signaling events and can be used as a primary factor for understanding the complex nature of this molecule. |
| first_indexed | 2024-03-09T06:14:59Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T06:14:59Z |
| publishDate | 2021-02-01 |
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| spelling | doaj.art-a38c9216b2fa4939bba628cc3da71dce2023-12-03T11:55:08ZengMDPI AGCells2073-44092021-02-0110351110.3390/cells10030511Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder CancerKirti Gondkar0Gajanan Sathe1Neha Joshi2Bipin Nair3Akhilesh Pandey4Prashant Kumar5Institute of Bioinformatics, International Tech Park, Bangalore 560066, IndiaInstitute of Bioinformatics, International Tech Park, Bangalore 560066, IndiaInstitute of Bioinformatics, International Tech Park, Bangalore 560066, IndiaAmrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, IndiaCenter for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, IndiaInstitute of Bioinformatics, International Tech Park, Bangalore 560066, IndiaDKK3 is a secreted protein, which belongs to a family of Wnt antagonists and acts as a potential tumor suppressor in gallbladder cancer. To further understand its tumor suppressor functions, we overexpressed DKK3 in 3 GBC cell lines. We have employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography to enrich phosphopeptides to check the downstream regulators. In this study, we reported for the first time the alteration in the phosphorylation of 14 kinases upon DKK3 overexpression. In addition, we observed DKK3 induced hyper phosphorylation of 2 phosphatases: PPP1R12A and PTPRA, which have not been reported previously. Canonical pathway analysis of altered molecules indicated differential enrichment of signaling cascades upon DKK3 overexpression in all the 3 cell lines. Protein kinase A signaling, Sirtuin signaling pathway, and Cell Cycle Control of Chromosomal Replication were observed to be differentially activated in the GBC cell lines. Our study revealed, DKK3 overexpression has differential effect based on the aggressive behavior of the cell lines. This study expands the understanding of DKK3-mediated signaling events and can be used as a primary factor for understanding the complex nature of this molecule.https://www.mdpi.com/2073-4409/10/3/511dickkopf homologue 3REICGBCserine-threonine phospho-proteomics |
| spellingShingle | Kirti Gondkar Gajanan Sathe Neha Joshi Bipin Nair Akhilesh Pandey Prashant Kumar Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer Cells dickkopf homologue 3 REIC GBC serine-threonine phospho-proteomics |
| title | Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer |
| title_full | Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer |
| title_fullStr | Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer |
| title_full_unstemmed | Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer |
| title_short | Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer |
| title_sort | integrated proteomic and phosphoproteomics analysis of dkk3 signaling reveals activated kinase in the most aggressive gallbladder cancer |
| topic | dickkopf homologue 3 REIC GBC serine-threonine phospho-proteomics |
| url | https://www.mdpi.com/2073-4409/10/3/511 |
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