SOX2 regulates melanoma initiating cells, study said

FLORENCE, ITALY – Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. Studies have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs).

Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2, a study by Barbara Stecca (Fiorgen Foundation and ITT, Istituto Toscano Tumori) said in Florence, Italy. The study, coordinated by professor Nicola Pimpinelli, was possible thanks to funding from the Ente Cassa di Risparmio di Firenze and it’s now published on Oncogene, a famous international scientific review.

The study addresses the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling.

SOX2 expression was investigated in 19 patient-derived primary melanoma cells, in A375 melanoma cell line and in normal human epidermal melanocytes. Quantitative real-time PCR revealed variable expression of SOX2; approximately half of the primary melanoma cultures showed high/intermediate levels and half no/very low expression, in line with previous immunohistochemistry studies.

SOX2 expression was documented at low levels in normal human epidermal melanocytes. Immunofluorescence analysis revealed SOX2 expression in the nuclei of primary melanoma cells. No significant correlation was found between SOX2 expression and tumor grade or other clinical features.

The study finds that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity.

Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDHhigh MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth.

 


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