ROLE OF SONIC HEDGEHOG PATHWAY IN CARCINOGENESIS: CANCER STEM CELLS, MULTIDRUG RESISTANCE, ANGIOGENESIS

Sonic Hedgehog pathway plays an important role in the formation and development of many types of cancer. Its biological significance is not fully understood. Cancer stem cell theory explains how SHH may influence on metastasis and self-renewal of cancer cells. Furthermore, it was discovered a strong link between SHH and vascular endothelial growth factor VEGF, which is essential for vascularization, and thus in promoting tumor growth and metastasis. The constitutive activation of Sonic Hedgehog pathway also contributes to resistance of tumors to treatment with cytostatics. Preliminary studies indicate that the high activity of SHH pathway is correlated with an increased expression of ABC transporter membrane proteins and reduced sensitivity of tumor cells towards therapeutics.