Metastasis accounts for about 90% of all cancer-related deaths, thus representing the largest problem of clinical oncology. Paracrine inflammatory signaling between tumor and immune cells significantly contributes to cancer progression. We discovered a specific subset of inflammatory genes that are up-regulated in highly metastatic mammary cells and repressed upon overexpression of transcription factor c-Myb. We propose to investigate how this transcriptional module regulated by c-Myb encodes functional programs of the inflammatory response, and how it participates in tumor-stroma cross-talk in metastasis. We postulate that c-Myb down-regulation releases high-risk inflammatory circuit that dictates metastatic site preference in basal-like breast cancer. We anticipate that implementation of this project will provide evidence for specific inflammation network facilitating lung seeding by breast cancer that could make the idea of targeting of tumor-stroma interaction in combination with chemotherapy in specific subset of breast carcinoma patients particularly engaging.

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