Abstract 1529: Role of bitter taste receptor in colon cancer

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the US with 53,200 deaths projected in 2020. Although the disease affects older people, recent statistics show an increase in the younger population. CRC is a major problem in veterans and every year ~4,000 veterans are diagnosed with CRC within VA facilities. Hence, there is a dire need to identify novel signaling pathways as targets for therapy. Based on a bedside discovery in CRC patients, we observed that CRC patients complained about dysgeusia or taste alterations. There are 25 bitter taste receptors (TAS2R1-50, TAS2R60). Taste receptors utilize G-protein coupled receptors (GPCRs) and signal through calcium release. In preliminary studies, mining the Cancer Genome Atlas (TCGA) database, we have determined that TAS2R38 is upregulated in multiple cancers, including CRC. Moreover, the higher expression of TAS2R38 transcript in CRC compared to other cancers. Furthermore, we confirmed overexpression of TAS2R38 in CRC tissues and cell lines by immunohistochemistry and RT-PCR. Moreover, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a TAS2R38 agonist, treatment activated calcium mobilization in HCT116 and DLD1 cells suggesting the functionality of the receptor. OdDHL also enhanced mRNA of interleukin (IL)-6 and IL-8 levels in the CRC cells. To determine whether expression of the receptor is affected in vivo, we conducted the dextran sodium sulfate (DSS)-induced acute colitis and colitis-associated cancer model (azoxymethane (AOM)-DSS) in C57BL/6 mice. TAS2R138, the mouse homolog of human TAS2R38 is overexpressed in crypt epithelial cells in the colitis and tumor tissues. These observations suggest that TAS2R38 is overexpressed in the CRC and may play a critical role in disease progression. Citation Format: Krishan Jain, Sangita Bhattacharyya, Afreen Sayed, David Standing, Kathy Benich, Shahid Umar, Shrikant Anant, Scott Weir, Roy Jansen, Prasad Ravindra Dandawate. Role of bitter taste receptor in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1529.