Abstract 6971: The impact of lecithin retinol acyltransferase in squamous cell carcinoma: Tissue formation, cell mechanics, and gene transcription

Abstract

Abstract Squamous cell carcinoma, along with several other cancers, has been found to lack expression of lecithin retinol acyltransferase (LRAT), a protein which catalyzes retinol esterification and thereby mediates retinoic acid biosynthesis. When expression of LRAT was reintroduced in squamous cell carcinoma, the protein promoted cell differentiation in addition to retinoid status normalization—whether this effect was dependent on the known enzymatic activity of LRAT in retinol esterification, versus another function, has not yet been established. Cell elasticity differences have also been reported between squamous cell carcinoma and normal keratinocytes. In this study, the role of LRAT expression and activity was evaluated in human squamous cell carcinoma cell line SCC13. LRAT was integrated into the genome of SCC13 via retroviral transduction, both as wild-type LRAT and LRAT with a cysteine-to-serine mutation at the active site for retinol esterification (C161-S). In these transformed cell lines, LRAT promoted formation of a cohesive sheet of tissue which remained intact after its removal from the tissue culture plastic surface, as evaluated at two weeks post-confluence. SCC13 alone produced tissue which easily fragmented during this scraping assay. In an evaluation of cell elasticity with shear modulation force microscopy, relative cell modulus measurements of pre-confluent SCC13 with LRAT expression were found to be significantly greater and consistent with the cell modulus of human keratinocytes (DO33). These effects persisted with mutation of the retinol esterification active site, suggesting that LRAT possesses an additional function which has yet to be described. Variation in transcription levels of multiple genes—urokinase-type plasminogen activator, plasminogen activator inhibitor 1, tissue inhibitor of metalloproteinases 1, and kallikrein 5—was also found based on LRAT expression and level of confluence. These findings suggest that the presence of LRAT influences tissue formation, cell elasticity, and gene transcription in SCC13. Citation Format: Emily Peterson, Kuan-Che Feng, Jay Gao, Miriam Rafailovich, Marcia Simon. The impact of lecithin retinol acyltransferase in squamous cell carcinoma: Tissue formation, cell mechanics, and gene transcription [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6971.