SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer

Table 4

Role of SOX9 and associated transcription factors in diverse types of cancer.

Type of cancer	TF	Effects	References
Breast cancer	SLUG (SNAI2)	Induction and maintenance of tumor initiating capacity in breast cancer cells	[58]
Breast cancer	TP53	Increased proliferation	[59–61]
Pancreatic cancer	HNF6 (ONECUT1)	Produces ectopic expression of Sox9 in acinar cells converting them in ductal cells	[34, 35]
Pancreatic cancer	NF-κB	NF-κB subunit p65 positively regulates SOX9 expression by directly binding to the SOX9 promoter	[40]
Pancreatic cancer	GLI1	Induces the transcription of SOX9	[62–66]
Pancreatic cancer	PDX1	Co-expressed in the cytoplasm with Sox9 in solid pseudopapillary tumors	[67, 68]
Prostate cancer	AR	Downstream target of SOX9	[69]
Prostate cancer	TCF4	It is positively regulated by SOX9	[70]
Prostate cancer	ZBTB7A (POKEMON)	It is lost in advance prostate cancer facilitating the oncogenic activity of SOX9	[71]
Ovarian cancer	HIF2A (EPAS1)	Hif-2α and Sox9 promote TUBB3 expression. High expression of TUBB3 and SOX9 correlates with shorter overall survival	[29]
Colorectal cancer	TCF4	Positively regulates SOX9	[72]
Colorectal cancer	PPARγ	In cell lines ligand-dependent PPARγ activation unevenly influences SOX9 and β-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis	[52]
Colorectal cancer	NF-Y	SOX9 is necessary for the function of NF-Y in activating expression of cyclin B1, cyclin B2, cyclin dependent kinase 1 and topoisomerase II α	[53]
Colorectal cancer	FOXK2	Is a SOX9 target and promotes proliferation	[54]