Abstract 1640: The role of CDC20 in the progression of colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is the one of most common cancers and a major leading cause of cancer-related death worldwide. CDC20 is a key cell cycle regulator required during mitosis. Pathologically, CDC20 has been found to be overexpressed in cancer cells of various malignancies including breast, lung, brain and hepatic cancers and high level of CDC20 expression is associated with poor prognosis and disease progression in these cancers. Although it has been reported that CDC20 is associated with CRC progression and metastasis, it is still largely unknown how CDC20 regulates CRC cancer progression. Thus, the goal of this study is to identify the role of CDC20 in the progression of colorectal cancer. Our gene expression analysis revealed that CDC20 is highly expressed in colon cancer tissues compared to their adjacent normal colon in a cohort of CRC patients, suggesting the involvement of CDC20 in the CRC progression. To further understand the role of CDC20 in CRC progression, we experimentally targeted CDC20 genetically and pharmacologically. To perform CDC20 Loss of function studies, we screened various CRC cell lines for CDC20 protein levels and CDC20 highly expressing cell lines were utilized to establish CDC20-knockdown cells using shRNA targeting CDC20 and scrambled shRNA as controls. CDC20 Down-regulation levels were confirmed using both western blot and RT-PCR analysis. The effect of CDC20 knockdown/CRC cells on CRC cell proliferation was investigated using xCELLigence real-time cell analysis instrument and colony formation assay. Our results revealed that CDC20 knockdown CRC cells have lower proliferation capacity compared to the control, suggesting involvement of CDC20 in regulating tumorigenic phenotypes of CRC cells. Pharmacologically, we targeted CDC20 using a specific molecular inhibitor, Apcin and we assessed the Apcin treatment effect on cell viability and migration of CRC cells. Our results showed that Apcin significantly reduced CRC cell viability and migration in a dose-dependent manner. Taken together, our results suggest that CDC20 is a key regulator in the tumorigenic behavior of CRC and is considered a potential therapeutic target for treating patients with CRC. Citation Format: Nouran Abualsaud, Nada Gazzaz, Amal Alhamid, Deemah Alenizy, Bahauddeen M. Alrfaei, Mana Alshehri. The role of CDC20 in the progression of colorectal cancer [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 1640.