Abstract 5142: Role of UCA1 in Warburg effect during anoikis resistance in colorectal carcinoma

Abstract Colorectal carcinoma (CRC) remains the second leading cause of cancer-related deaths in the United States. The survival rate for CRC patients drops precipitously from 90% for localized disease to only 14% upon metastasis. Approximately, 40-50% of CRC cases progress to metastasis, a multifaceted process requiring the acquisition of anoikis resistance as one of the critical steps. This anoikis or anchorage-independent resistance enables cancer cells to survive detachment from the extracellular matrix, migrate through vascular and lymphatic systems, and establish secondary tumor sites. A deeper understanding of the molecular mechanisms underlying anoikis resistance, particularly in the context glucose metabolism, is crucial for advancing therapeutic strategies in CRC metastasis. Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation characterized by preferential glycolysis over oxidative phosphorylation, even under normoxic conditions. This metabolic reprogramming supports proliferation and may promote survival under anchorage-independent conditions. Our preliminary data suggests that the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1), which is overexpressed in CRC and correlates with poor prognosis, may play a pivotal role in metastasis and glucose metabolism. Utilizing isogenic a CRC cell line model SW480 (primary tumor-derived) and SW620 (metastasis-derived), we have developed stable UCA1-overexpressing (SW480+UCA1) and UCA1-knockdown (SW620+shUCA1) experimental models. In vitro characterization of the cell lines via phenotypic assays showing invasion, migration, and cell proliferation by xcelligence and colony formation to be enhanced through UCA1 overexpression and reduced by its knockdown. Furthermore, our data indicates that UCA1 overexpression enhances glucose uptake, lactate production, and anchorage-independent survival, suggesting its involvement in promoting anoikis resistance through metabolic reprogramming. Moreover, these cell lines will be subjected to anchorage-independent growth conditions to assess alterations in cell cycle, pro-survival, and stemness-related markers. Furthermore, glucose metabolism will be evaluated using Seahorse XFp metabolic analysis parameters. Citation Format: Ricardo Pequeno Bracho, Salique H. Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Bilal B. Hafeez, Tamer Oraby, Subhash C. Chauhan, Manish K. Tripathi. Role of UCA1 in Warburg effect during anoikis resistance in colorectal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5142.