Abstract 3595: Epigenetic driven IL32 expression contributes to a JNK related cell stress response in breast cancer stem cells to promote cellular invasion - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2023

Abstract 3595: Epigenetic driven IL32 expression contributes to a JNK related cell stress response in breast cancer stem cells to promote cellular invasion

Megan Wilson
  • Fonction : Auteur
Elayne Benson
  • Fonction : Auteur
Emma Gray
  • Fonction : Auteur
Paige Cairns
  • Fonction : Auteur
Hasan Korkaya
  • Fonction : Auteur
Austin Shull
  • Fonction : Auteur

Résumé

Abstract Metastatic potential in basal-like breast cancers typically correspond with increased enrichment of EpCAM-/CD49f- cancer stem cells (CSC). With this premise in mind, it is important to better understand the mechanistic driver of these cell populations and their distinctive potential to interact with the tumor microenvironment (TME) for cancer promotion. Previous work from our lab has compared the 450K DNA methylation profile of EpCAM-/CD49f- poor breast cancer cell lines to that of EpCAM-/CD49f- enriched breast cancer cell lines and found the IL32 promoter to be hypomethylated in EpCAM-/CD49f- enriched cell lines, a result which corresponded basal-like patient samples in TCGA. By identifying IL32 being differentially regulated in CSC-enriched cell lines, we further sought to characterize IL32’s role in breast cancer aggressiveness. We first were able to identify several overarching mechanisms altered in siIL32 treated SUM15PT cells by RNAseq differential expression analysis (FDR p-value <0.01). Most notable from our RNAseq results was the significant enrichment of upregulated pathways involved in extracellular matrix (ECM) organization as well as significant enrichment of downregulated pathways involved in cellular and replicative stress responses. Particular examples of transcripts differentially expressed between control and siIL32-treated SUM159PT cells included COL6A1, ITGB3, and CD24 that were upregulated as well as NQO1, HMOX1, and CXCL2/CXCL3 that were downregulated. Furthermore, IL32 suppression decreased SUM159PT invasion in both an ECM-matrix cell invasion assay and a chick CAM xenograft/angiogenesis model. From our RNAseq results, we then performed a multi-pathway protein phosphorylation array to determine whether any key signaling events were affected by siIL32 knockdown in SUM159PT cells. Based on this approach, we were able observe a significant decrease in phosphorylated JNK and phosphorylated NFKB in siL32-treated cells when compared to control, both of which are well-established events that can coordinate both cell stress responses and cellular invasion. Collectively, our results reflect the notion that differential IL32 expression by promoter hypomethylation in breast CSCs plays a role to mitigating intracellular stress and subsequently allowing for breast cancer cell invasion and metastasis. Citation Format: Megan A. Wilson, Elayne M. Benson, Emma Gray, Paige Cairns, Maria Ouzounova, Hasan Korkaya, Austin Y. Shull. Epigenetic driven IL32 expression contributes to a JNK related cell stress response in breast cancer stem cells to promote cellular invasion. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3595.
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Dates et versions

hal-04104598 , version 1 (24-05-2023)

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Megan Wilson, Elayne Benson, Emma Gray, Paige Cairns, Maria Ouzounova, et al.. Abstract 3595: Epigenetic driven IL32 expression contributes to a JNK related cell stress response in breast cancer stem cells to promote cellular invasion. American Association for Cancer Research Annual Meeting 2023, American Association for Cancer Research, Apr 2023, Orlando, United States. pp.3595-3595, ⟨10.1158/1538-7445.AM2023-3595⟩. ⟨hal-04104598⟩
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