Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
09 11 2023
Historique:
received: 25 11 2021
accepted: 26 10 2023
medline: 13 11 2023
pubmed: 10 11 2023
entrez: 9 11 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37945749
doi: 10.1038/s42003-023-05510-w
pii: 10.1038/s42003-023-05510-w
pmc: PMC10636189
doi:

Substances chimiques

Succinate Dehydrogenase EC 1.3.99.1
Flavin-Adenine Dinucleotide 146-14-5
SDHA protein, human EC 1.3.5.1
Electron Transport Complex II EC 1.3.5.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1134

Subventions

Organisme : NCI NIH HHS
ID : R01 CA182043
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2023. The Author(s).

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Auteurs

Tomoko Marumo (T)

Department of Oral and Maxillofacial Surgery, Tokyo Dental College, 2-9-18 Kanda-Misakicho, Chiyoda-ku, Tokyo, 101-0061, Japan.
Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA.

Chima V Maduka (CV)

Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Comparative Medicine & Integrative Biology, Michigan State University, East Lansing, MI, 48824, USA.
BioFrontiers Institute, University of Colorado, Boulder, CO, 80303, USA.

Evran Ural (E)

Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA.

Ehsanul Hoque Apu (EH)

Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Division of Hematology and Oncology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Seock-Jin Chung (SJ)

Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA.

Koji Tanabe (K)

Department of Biomedical Engineering, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.

Nynke S van den Berg (NS)

Department of Otolaryngology - Division of Head and Neck Surgery, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA, 94305, USA.

Quan Zhou (Q)

Department of Otolaryngology - Division of Head and Neck Surgery, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA, 94305, USA.

Brock A Martin (BA)

Department of Pathology, Stanford University School of Medicine, 3100 Pasteur Drive, Stanford, CA, 94305, USA.

Tadashi Miura (T)

Oral Health Science Center, Tokyo Dental College, 2-1-14 Kanda-Misakicho, Chiyoda-ku, Tokyo, 101-0061, Japan.

Eben L Rosenthal (EL)

Department of Otolaryngology - Division of Head and Neck Surgery, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA, 94305, USA.
Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, 37232, USA.

Takahiko Shibahara (T)

Department of Oral and Maxillofacial Surgery, Tokyo Dental College, 2-9-18 Kanda-Misakicho, Chiyoda-ku, Tokyo, 101-0061, Japan.

Christopher H Contag (CH)

Department of Biomedical Engineering, Michigan State University, East Lansing, MI, 48824, USA. contagch@msu.edu.
Institute for Quantitative Health Science & Engineering, Michigan State University, East Lansing, MI, 48824, USA. contagch@msu.edu.
Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA. contagch@msu.edu.

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