SOX2 mediates crosstalk between Sonic Hedgehog and the Wnt/β-catenin signaling pathway to promote proliferation of pituitary adenoma cells.

The Sonic hedgehog (Shh) and Wnt/β-catenin signaling pathways are important regulators of early tissue patterning and stem cell propagation, and aberrant regulation of these two signaling pathways has been associated with a number of types of cancer. The identification of adult stem cells in the pituitary raised the question of whether these two signaling pathways are involved in pituitary adenoma formation. In the present study, it was identified that treating a human pituitary adenoma cell line with Shh was not able to promote the proliferation of cancer cells, but Shh was able to upregulate the expression of sex-determining region Y box 2 (SOX2) which is characteristic of stem cells. The addition of Shh into β-catenin-expressing cells also promoted cell proliferation. On the other hand, addition of Wnt3a into or overexpression of β-catenin in SOX2-expressing cancer cells was able to promote cell proliferation, Further investigation revealed that SOX2 is required to mediate crosstalk between the Shh and Wnt/β-catenin signaling pathways to promote the proliferation of pituitary adenoma cells.