Tetraspanin CD82 Correlates with and May Regulate S100A7 Expression in Oral Cancer

Author:

Reddi Kiran Kumar1ORCID,Zhang Weiqiang234ORCID,Shahrabi-Farahani Shokoufeh5ORCID,Anderson Kenneth Mark5ORCID,Liu Mingyue1ORCID,Kakhniashvili David6ORCID,Wang Xusheng7ORCID,Zhang Yanhui H.1ORCID

Affiliation:

1. Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, 875 Union Ave, Memphis, TN 38163, USA

2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA

3. Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA

4. USDA-ARS, Pollinator Health in Southern Crop Ecosystem Research Unit, 141 Experiment Station Road, P.O. Box 346, Stoneville, MS 38776, USA

5. Department of Diagnostic Sciences, College of Dentistry, University of Tennessee Health Science Center, 875 Union Ave, Memphis, TN 38163, USA

6. The Proteomics & Metabolomics Core Facility, University of Tennessee Health Science Center, 71 S. Manassas, Suite 110, Memphis, TN 38163, USA

7. Department of Genetics, Genomics & Informatics, University of Tennessee Health Science Center, 71 S. Manassas, Room 410H, Memphis, TN 38163, USA

Abstract

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37–50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Funder

University of Tennessee Health Science Center

UT Health Science Center College of Dentistry Alumni Endowment Fund

Tennessee Dental Association Foundation

U.S. National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health

Publisher

MDPI AG

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