Notch1-MAPK signaling axis is essential in CD133+ melanoma initiating cells.

Human malignant melanoma is highly aggressive and metastatic in nature and exhibits phenotypic plasticity. Melanoma has multiple phenotypically distinct subpopulations which involved in tumor progression and markedly resistant to conventional therapy. Some of the melanoma subpopulation exhibits stem cells feature and defined as cancer stem cells (CSCs) or tumor initiating cells (TICs). Identification and characterization of CSCs in melanoma may have therapeutic implication for combating melanoma progression. In recent study, we have identified that CD133+ subpopulation of melanoma potentially involved in tumor initiation, metastasis, epithelial to mesenchymal (EMT) and angiogenesis. Genetic and pharmacological screening revealed that functional properties of CD133+ melanoma cells are regulated by Notch1-MAPK signaling axis. Andrographolide (herbal product) abrogates Notch1-MAPK pathway in CD133+ cells that leads to attenuation of melanoma progression, metastasis and angiogenesis.