Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations
Abstract Kindlins serve as mechanosensitive adapters, transducing extracellular mechanical cues to intracellular biochemical signals and thus, their perturbations potentially lead to cancer progressions. Despite the kindlin involvement in tumor development, understanding their genetic and mechanoche...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-06044-5 |
| _version_ | 1797233387604279296 |
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| author | Debojyoti Chowdhury Ayush Mistry Debashruti Maity Riti Bhatia Shreyansh Priyadarshi Simran Wadan Soham Chakraborty Shubhasis Haldar |
| author_facet | Debojyoti Chowdhury Ayush Mistry Debashruti Maity Riti Bhatia Shreyansh Priyadarshi Simran Wadan Soham Chakraborty Shubhasis Haldar |
| author_sort | Debojyoti Chowdhury |
| collection | DOAJ |
| description | Abstract Kindlins serve as mechanosensitive adapters, transducing extracellular mechanical cues to intracellular biochemical signals and thus, their perturbations potentially lead to cancer progressions. Despite the kindlin involvement in tumor development, understanding their genetic and mechanochemical characteristics across different cancers remains elusive. Here, we thoroughly examined genetic alterations in kindlins across more than 10,000 patients with 33 cancer types. Our findings reveal cancer-specific alterations, particularly prevalent in advanced tumor stage and during metastatic onset. We observed a significant co-alteration between kindlins and mechanochemical proteome in various tumors through the activation of cancer-related pathways and adverse survival outcomes. Leveraging normal mode analysis, we predicted structural consequences of cancer-specific kindlin mutations, highlighting potential impacts on stability and downstream signaling pathways. Our study unraveled alterations in epithelial–mesenchymal transition markers associated with kindlin activity. This comprehensive analysis provides a resource for guiding future mechanistic investigations and therapeutic strategies targeting the roles of kindlins in cancer treatment. |
| first_indexed | 2024-04-24T16:15:22Z |
| format | Article |
| id | doaj.art-4f547df8398743b9b7ffee5d49b5104d |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-24T16:15:22Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-4f547df8398743b9b7ffee5d49b5104d2024-03-31T11:28:59ZengNature PortfolioCommunications Biology2399-36422024-03-017111610.1038/s42003-024-06044-5Pan-cancer analyses suggest kindlin-associated global mechanochemical alterationsDebojyoti Chowdhury0Ayush Mistry1Debashruti Maity2Riti Bhatia3Shreyansh Priyadarshi4Simran Wadan5Soham Chakraborty6Shubhasis Haldar7Department of Chemical and Biological Sciences, S.N. Bose National Centre for Basic SciencesDepartment of Biology, Trivedi School of Biosciences, Ashoka UniversityDepartment of Chemical and Biological Sciences, S.N. Bose National Centre for Basic SciencesDepartment of Biology, Trivedi School of Biosciences, Ashoka UniversityDepartment of Biology, Trivedi School of Biosciences, Ashoka UniversityDepartment of Biology, Trivedi School of Biosciences, Ashoka UniversityDepartment of Biology, Trivedi School of Biosciences, Ashoka UniversityDepartment of Chemical and Biological Sciences, S.N. Bose National Centre for Basic SciencesAbstract Kindlins serve as mechanosensitive adapters, transducing extracellular mechanical cues to intracellular biochemical signals and thus, their perturbations potentially lead to cancer progressions. Despite the kindlin involvement in tumor development, understanding their genetic and mechanochemical characteristics across different cancers remains elusive. Here, we thoroughly examined genetic alterations in kindlins across more than 10,000 patients with 33 cancer types. Our findings reveal cancer-specific alterations, particularly prevalent in advanced tumor stage and during metastatic onset. We observed a significant co-alteration between kindlins and mechanochemical proteome in various tumors through the activation of cancer-related pathways and adverse survival outcomes. Leveraging normal mode analysis, we predicted structural consequences of cancer-specific kindlin mutations, highlighting potential impacts on stability and downstream signaling pathways. Our study unraveled alterations in epithelial–mesenchymal transition markers associated with kindlin activity. This comprehensive analysis provides a resource for guiding future mechanistic investigations and therapeutic strategies targeting the roles of kindlins in cancer treatment.https://doi.org/10.1038/s42003-024-06044-5 |
| spellingShingle | Debojyoti Chowdhury Ayush Mistry Debashruti Maity Riti Bhatia Shreyansh Priyadarshi Simran Wadan Soham Chakraborty Shubhasis Haldar Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations Communications Biology |
| title | Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations |
| title_full | Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations |
| title_fullStr | Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations |
| title_full_unstemmed | Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations |
| title_short | Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations |
| title_sort | pan cancer analyses suggest kindlin associated global mechanochemical alterations |
| url | https://doi.org/10.1038/s42003-024-06044-5 |
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