Abstract 544: Role of an ankyrin domain protein in hepatocellular carcinoma progression

Abstract

Abstract Background: Liver cancer is the third leading cause of mortality attributed to cancer. Hepatocellular carcinoma (HCC) is the most prevalent form among various histological types accounting for 85% to 90% of primary liver cancers. As per Texas Cancer Registry, the Hispanic population had an incidence of 21.2 per 100,000 in Texas. The Rio Grande Valley, located in South Texas, is an underserved area composed highly of Hispanics. It faces multiple disparities that can attribute to increased risk factors of HCC and, thus, a higher liver cancer incidence and mortality. Due to this, there is a need to identify a new, inexpensive, and faster diagnostic biomarker in liver cancer. We have recently identified an extracellular secreted cancer antigen POTE-2, a member of the ankyrin domain-containing POTE gene family. Our preliminary data indicates high POTE-2 expression in HCC tumors. In this study, we will discuss the role of POTE-2 in HCC progression and its associated regulatory pathways. Methods: The Cancer Genome Atlas (TCGA) database of HCC patients (n=371 tumor; n=50 normal) was analyzed. Liver cancer cell lines procured from ATCC were analyzed for POTE-2 mRNA and protein expression through RT-PCR and western blot, respectively. Lentiviral-based plasmids were used for overexpression and knockdown studies for oncogenic assays. Localization of POTE-2, YAP1, and PDL1 was identified with immunofluorescence. Results: Comprehensive analysis of the TCGA database showed increased POTE-2 expression in tumors and is upregulated in all stages of HCC. Lentiviral transduction led to a change in phenotype in oncogenic assays. Modulation of POTE-2 expression led to changes in kinase activity and regulatory pathways. Immunofluorescence showed nuclear localization of YAP1 and PDL1 in the liver cancer cell lines. Conclusion: These studies will help discover novel mechanisms of POTE-2 protein function, signaling pathways, and its role in liver cancer progression. Citation Format: Samantha Lopez, Adithya Anilkumar, Kyle Doxtater, Sudhir Kotnala, Neeraj Chauhan, Murali Yallapu, Meena Jaggi, Subhash Chauhan, Manish Tripathi. Role of an ankyrin domain protein in hepatocellular carcinoma progression [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 544.