Identification and analysis of CD133+ melanoma stem-like cells conferring resistance to taxol: An insight into the mechanisms of their resistance and response

• Cancer stem-like cells (CSCs) are responsible for tumor initiation and progression.
• We characterized the molecular mechanisms of melanoma stem-like cells (MSCs) resistance to taxol.
• The analysis of the resistant mechanisms is important for the development of an efficient therapy.
• The combination of ERK inhibitor with taxol, or Bax gene transfer overcome MSCs resistance to taxol.
• Our data suggest relevant strategy for the treatment of melanoma metastasis.

The presence and the involvement of cancer stem-like cells (CSCs) in tumor initiation and progression, and chemo-resistance are documented. Herein, we functionally analyzed melanoma stem-like cells (MSC)/CD133+ cells on their resistance and response to taxol-induced apoptosis. Besides being taxol resistant, the CD133+ cells demonstrated a growth advantage over the CD133− subpopulation. Taxol induced apoptosis on CD133− cells, but not on CD133+ cells. In the CD133− subpopulation, the exposure to taxol induced the activation of apoptosis signal-regulating kinase1 (ASK1)/c-jun-N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK) pathways and Bax expression, while in CD133+ cells taxol was able only to enhance the activity of the ERK pathway. In CD133+ cells, the direct gene transfer of Bax overcame the acquired resistance to taxol. Taken together, our data provide an insight into the mechanistic cascade of melanoma resistance to taxol and suggest Bax gene transfer as a complementary approach to chemotherapy.