RIPK2: New Elements in Modulating Inflammatory Breast Cancer Pathogenesis

Autor: Heather Amstrong, Katia Tonkin, Alaa Zare, Shairaz Baksh, A Petrova, Mehdi Agoumi, Gilbert Bigras, Eytan Wine
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cancers, Vol 10, Iss 6, p 184 (2018)
Cancers
Volume 10
Issue 6
ISSN: 2072-6694
Popis: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that is associated with significantly high mortality. In spite of advances in IBC diagnoses, the prognosis is still poor compared to non-IBC. Due to the aggressive nature of the disease, we hypothesize that elevated levels of inflammatory mediators may drive tumorigenesis and metastasis in IBC patients. Utilizing IBC cell models and patient tumor samples, we can detect elevated NF-&kappa
B activity and hyperactivation of non-canonical drivers of NF-&kappa
B (nuclear factor kappaB)-directed inflammation such as tyrosine phosphorylated receptor-interacting protein kinase 2 (pY RIPK2), when compared to non-IBC cells or patients. Interestingly, elevated RIPK2 activity levels were present in a majority of pre-chemotherapy samples from IBC patients at the time of diagnosis to suggest that patients at diagnosis had molecular activation of NF-&kappa
B via RIPK2, a phenomenon we define as &ldquo
molecular inflammation&rdquo
Surprisingly, chemotherapy did cause a significant increase in RIPK2 activity and thus molecular inflammation suggesting that chemotherapy does not resolve the molecular activation of NF-&kappa
B via RIPK2. This would impact on the metastatic potential of IBC cells. Indeed, we can demonstrate that RIPK2 activity correlated with advanced tumor, metastasis, and group stage as well as body mass index (BMI) to indicate that RIPK2 might be a useful prognostic marker for IBC and advanced stage breast cancer.
Databáze: OpenAIRE
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