Research Activities

The c-Myb signaling in control of tumorigenesis and metastasis

c-Myb is a transcription factor that regulates stem and progenitor cells in bone marrow, colonic crypts and neurogenic niches of adult brain. As a regulator of stem-progenitor cells, c-Myb is involved in control of an exquisite balance between cell proliferation, differentiation and survival. When aberrantly activated, c-Myb induces expression of target genes that disturb the balance in favor of proliferation and survival thus contributing to malignant transformation. The c-Myb malfunction is well-known in leukemias but it is also involved in several epithelial cancers, including breast and colorectal cancer.

While the role of the Myb proteins in stimulation of proliferation, suppression of differentiation and apoptosis has been studied in cancer cells for decades, current knowledge on the role of c-Myb in control of metastasis formation remains poor. Therefore, our research focuses on the function of the c-Myb and its signaling network in control of tumor metastasis and tumor-stromal interactions.

Tumor microenvironment and its modulation in cancer therapy

The tumor microenvironment, composed of malignant and stromal cells has become recognized as a key factor affecting tumor growth and progression. Stromal and other non-malignant cells create microenvironment supporting tumor growth, metastasis and resistance to therapy. The metabolic environment of the tumor is furthermore affected by functionally compromised vasculature and subsequent nutrients starvation, hypoxia and acidosis.Targeting the components of the tumor microenvironment has emerged as a promising approach of anti-cancer therapies. In our laboratory, we investigate tumor-stromal interactions using 2D and 3D cell culture methods and mouse models with the aim to identify key cancer progression-related cell-cell signaling pathways and novel cancer therapeutic targets.

The tumor-specific microenvironment can also affect the distribution and the efficacy of anti-cancer drugs. We are developing and optimizing new aproaches for cultivation and analysis of 3D tumor models (spheroids and organotypic slice cultures). We have recently introduced a state-of-the-art methodology for the detection of drug distribution and its correlation with morphological and molecular changes of tumor/stromal cells in these models. The results of this research should contribute to development of new personalized treatment strategies of oncological patients.

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Organizational structure:
Masaryk UniversityFaculty of ScienceDepartment of Experimental BiologySection of Genetics and Molecular BiologyLaboratory of Cell Differentiation

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