Trop-2 in Breast Cancer Adaptation to Specific Conditions of Tumor Microenvironment

The ability of tumor cells to adapt to dynamic microenvironment is considered a key requirement for their growth, survival and dissemination. One of the molecules that may interlink processes of plasticity of cancer cells, their dissemination capability and adaptation to microenvironmental factors is the transmembrane glycoprotein Trop-2. This protein is often associated with regulation of cell proliferation, survival, tumorigenicity and cancer progression, however, the specific function of Trop-2 during tumorigenesis and metastasis has not been yet fully elucidated. Here we analyzed the molecular basis of Trop-2 expression and function in the context of dynamic tumor/metastatic microenvironment. We observed a dramatic decrease in the frequency of Trop2 positive cells in breast cancer cells exposed to repeated cycling of hypoxia/starvation. Furthermore, we found that cells with low or no expression of Trop2 are significantly more resistant to these tumor microenvironment-like conditions and that Trop2 expression is regulated by both environmental factors. Moreover, we identified JNK/AP-1 signaling as an important regulator of Trop2 expression/function in breast cancer cells. These results demonstrate that Trop2-mediated signaling affect breast cancer cell adaptation to specific conditions of tumor/metastatic microenvironment.

This work was funded by grant NT 13441-4/2012 of the Internal Grant Agency of Ministry of Health of the Czech Republic, by the European Regional Development Fund Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) and by FP7 REGPOT project ICRC-ERA-HumanBridge (no. 316345).