Abstract 5324: Key antiviral response genes mediate the impact of chromosomal instability on breast cancer stemness

Abstract Chromosomal instability (CIN) is a recognized hallmark of cancer, pivotal in tumor evolution and metastasis. Our research unveils CIN as a stress during tumor initiation, uniquely tolerated by activated breast cancer stem cells (aCSCs). Elevated CIN, specific to tumors from aCSCs, contrasts with baseline levels akin to non-stem cell types. This transient increase in CIN, observed in low burden aCSC tumors, diminishes in established disease, suggesting a dynamic induction during initiation. Consist wit this we have observed increase in CIN tolerance in stem-like vs basal-like cells suggesting heterogeneity in response. CIN triggers a specific response, activating proinflammatory cancer autonomous immune signaling. We identified several CIN-induced proinflammatory stem cell-specific genes from our overlap studies. Knockdown assays targeting RSAD2 and PLAU showed a significant decrease in tumorsphere properties, emphasizing their functional relevance for cancer progression. AXL did not show any effect on tumorsphere but was important to tolerate CIN induced due to reversine. Mechanistically, AXL expression was induced by c-Jun stress signaling activation in aCSCs. These antiviral CIN-induced proinflammatory markers, emerge as a vital player in breast cancer progression. This study establishes a foundation for investigating antiviral genes as crucial contributors to cancer. Citation Format: Shahnawaz A. Baba, Samson Mugisha, Shreyas labhsetwar, Richard klemke, Jay Desgrosellier. Key antiviral response genes mediate the impact of chromosomal instability on breast cancer stemness 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 (6Suppl): Abstract nr 5324.