Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers
Abstract The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05510-w |
| _version_ | 1797630061081264128 |
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| author | Tomoko Marumo Chima V. Maduka Evran Ural Ehsanul Hoque Apu Seock-Jin Chung Koji Tanabe Nynke S. van den Berg Quan Zhou Brock A. Martin Tadashi Miura Eben L. Rosenthal Takahiko Shibahara Christopher H. Contag |
| author_facet | Tomoko Marumo Chima V. Maduka Evran Ural Ehsanul Hoque Apu Seock-Jin Chung Koji Tanabe Nynke S. van den Berg Quan Zhou Brock A. Martin Tadashi Miura Eben L. Rosenthal Takahiko Shibahara Christopher H. Contag |
| author_sort | Tomoko Marumo |
| collection | DOAJ |
| description | Abstract The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region, with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients. |
| first_indexed | 2024-03-11T11:02:43Z |
| format | Article |
| id | doaj.art-db37e6deb74d46b8a147fa7635fece47 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-11T11:02:43Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-db37e6deb74d46b8a147fa7635fece472023-11-12T12:27:17ZengNature PortfolioCommunications Biology2399-36422023-11-016111310.1038/s42003-023-05510-wFlavinated SDHA underlies the change in intrinsic optical properties of oral cancersTomoko Marumo0Chima V. Maduka1Evran Ural2Ehsanul Hoque Apu3Seock-Jin Chung4Koji Tanabe5Nynke S. van den Berg6Quan Zhou7Brock A. Martin8Tadashi Miura9Eben L. Rosenthal10Takahiko Shibahara11Christopher H. Contag12Department of Oral and Maxillofacial Surgery, Tokyo Dental CollegeDepartment of Biomedical Engineering, Michigan State UniversityDepartment of Biomedical Engineering, Michigan State UniversityDepartment of Biomedical Engineering, Michigan State UniversityDepartment of Biomedical Engineering, Michigan State UniversityDepartment of Biomedical Engineering, Iwate Medical UniversityDepartment of Otolaryngology – Division of Head and Neck Surgery, Stanford University School of MedicineDepartment of Otolaryngology – Division of Head and Neck Surgery, Stanford University School of MedicineDepartment of Pathology, Stanford University School of MedicineOral Health Science Center, Tokyo Dental CollegeDepartment of Otolaryngology – Division of Head and Neck Surgery, Stanford University School of MedicineDepartment of Oral and Maxillofacial Surgery, Tokyo Dental CollegeDepartment of Biomedical Engineering, Michigan State UniversityAbstract The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region, with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.https://doi.org/10.1038/s42003-023-05510-w |
| spellingShingle | Tomoko Marumo Chima V. Maduka Evran Ural Ehsanul Hoque Apu Seock-Jin Chung Koji Tanabe Nynke S. van den Berg Quan Zhou Brock A. Martin Tadashi Miura Eben L. Rosenthal Takahiko Shibahara Christopher H. Contag Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers Communications Biology |
| title | Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers |
| title_full | Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers |
| title_fullStr | Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers |
| title_full_unstemmed | Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers |
| title_short | Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers |
| title_sort | flavinated sdha underlies the change in intrinsic optical properties of oral cancers |
| url | https://doi.org/10.1038/s42003-023-05510-w |
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