Elucidating the role of receptor-interacting protein kinase 2 in inflammatory breast cancer
Loading...
Authors
Ojobile, Innocent
Date
2025-08-27
Type
thesis
Language
eng
Keyword
Receptor interacting protein kinase 2 , Inflammatory breast cancer , Hybrid epihelial-mesenchymal transition
Alternative Title
Abstract
Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer (BC). It constitutes approximately 2% of all BC cases yet causes nearly 10% of all BC deaths. The median overall survival of IBC patients relative to non-IBC is 4 years versus 10 years for non-IBC at stage III, and 2 years at stage IV, versus 5 years for non-IBC. The current treatment strategy involves surgery, chemotherapy and radiotherapy. However, despite the multimodality, the survival rates are still poor. Therefore, this unique, highly lethal subtype of BC requires more effective treatment to improve survival outcomes in the IBC cells. Receptor-interacting protein kinase 2 (RIPK2), a threonine/serine kinase protein, is a downstream signalling molecule of the nucleotide oligomerisation domain 2 (NOD2) and has been implicated in the aggressive nature of IBC. RIPK2 plays a crucial role as a mediator of inflammatory responses by activating the NF-κB pathway downstream, leading to the transcription of pro-inflammatory cytokines. Previous studies have indicated that RIPK2 regulates the progression of IBC through NF-κB, which promotes the expression of pro-inflammatory cytokines such as IL-1β and IL-6, ultimately leading to the highly proliferative, metastatic, and angiogenic phenotypes characteristic of IBC. Herein, I demonstrate that RIPK2 enhances 3D invasion in IBC cell lines, concomitant with an increase in the expression of hybrid epithelial-to-mesenchymal transition (EMT) markers; a mechanism by which cells retain both epithelial and mesenchymal traits. Collectively, our results suggest that RIPK2 may be a promising target for the treatment of IBC.