Influence of transforming growth factor-b1-induced epithelial-mesenchymal transition on breast cancer cell metastasis through lymphatic system

• Applicant: Dr. Wenwen Sun
• Subject Area: Hematology, Oncology ; Anatomy and Physiology ; Gynaecology and Obstetrics ; Cell Biology
• Term: from 2018 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407529432

Reactivation of epithelial-mesenchymal transition (EMT) is identified as a potential driving force for cancer metastasis. Cancer cells undergoing EMT generally show loss of cellular junction and enhanced migratory ability. However, different EMT activators operate through different signaling pathways. The research group of Prof. Jonas Fuxe (Solna, Sweden) recently demonstrated that genetically altered breast cancer cells which are stably in autocrine TGF-b1-induced EMT (abbreviated as EMT cells) show markedly higher tendency to migrate into lymphatic vessels and to draining lymph nodes, but not into blood vessels, indicating that presence of TGF-b1-induced EMT might have a major importance specifically in breast cancer patients with high rate of lymph node metastasis. However, whether EMT cells are in the position to migrate further into systemic circulation and whether they finally colonize in distant organs still need to be studied. In this project, two-photon microscopy will be conducted in collaboration with Prof. Santiago Gonzalez (Bellinzona, Switzerland) to determine how EMT cells migrate after entering draining lymph nodes. Furthermore, involvement of anthrax toxin receptor 2 in TGF-b1-induced EMT and its potential clinical significance in breast cancer will be analyzed. The purpose of the project is to characterize the possibly underestimated role of TGF-b1-induced EMT in breast cancer patients with high rate of lymph node metastasis and to identify further potential therapeutic targets.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professor Dr. Jonas Fuxe