TABLE 3.

Common functions and pathways of SIX family genes in development and cancer biology.

Gene	Functions in development	Functions in cancer	Common pathways	Cell cycle targets
SIX1	Progenitor cell maintenance, proliferation, cell differentiation, muscle cell migration	Proliferation, stem cell self-renewal, EMT, metastasis	Wnt/β-catenin, Notch, TGF-β	Cyclin A Cyclin D
SIX2	Progenitor cell maintenance, proliferation, cell differentiation promotion of mesenchymal phenotype	Proliferation, stem cell self-renewal, EMT, metastasis	Wnt/β-catenin, Notch, potentially TGF-β	Cyclin D
SIX3	Progenitor cell maintenance, cell differentiation	Suppression of cell proliferation; reduced EMT and tumor invasion	Wnt/β-catenin, Notch	Cyclin A
SIX4	Cooperative interaction with other SIX transcription factors	Proliferation, EMT, migration, metastasis	Potentially Wnt/β-catenin, TGF-β	Indirect regulation through c-Met
SIX5	Cell differentiation	ND	ND	ND
SIX6	Proliferation	ND	Wnt/β-catenin, Notch	P27

See text for details and references.

ND, not determined.