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

Table 2

Sox9 is expressed during premalignant and malignant lesions in pancreatic cancer.

Lesions	Model	Status of SOX9	Effects	References
Acinar-to-ductal metaplasia	Mice	Overexpressed	HNF6 induces Sox9 expression, which is characteristic of ADM in humans	[34, 35]
Acinar-to-ductal metaplasia	Mice	Overexpressed	Aberrant expression of p27 induces the nuclear expression of Sox9	[36]
Mucinous cystic neoplasias, intraductal papillary mucinous neoplasias, pancreatic intraepithelial neoplasias and pancreatic ductal adenocarcinoma	Mice	Overexpressed	SOX9 and Kras co-expression is associated with PDAC initiation	[37]
Pancreatic ductal adenocarcinoma	88 tumors samples of PDAC	Overexpressed	Sox9 and p-Akt double-positive expression is related with an unfavorable prognosis, high TNM and distant metastasis	[38]
Pancreatic ductal adenocarcinoma	Patient-derived tumor organoids with PDAC	Overexpressed in cytoplasm	High expression of Sox9 in cytoplasm is related with a poor DFS, OS, higher tumor grade and worse disease-specific survival compared to patients with nuclear Sox9 expression	[39]
Pancreatic cancer	PANC1 and HPAC cell lines of pancreatic cancer	Overexpressed	Sox9 is highly expressed in pancreatic CSCs. Moreover, NF-κB subunit p65 positively regulates SOX9	[40]
Pancreatic ductal adenocarcinoma	HD3 colon cancer cells	Overexpressed	ST6Gal-I induces expression of Sox9, promoting stem-like cell properties	[41]
Pancreatic cancer	PANC-1, Capan-1, BxPC-3, MiaPaCa-2 cell lines of pancreatic cancer	Expression depending on chemoresistance	High level of Sox9 is related to stronger chemoresistance to Gemcitabine	[42]
Pancreatic ductal adenocarcinoma	HPDE cell line of PDAC	Overexpressed	GLI1 induces the transcription of Sox9 promoting stem cell properties	[43]
Pancreatic cancer	PANC1 cell line of pancreatic cancer	Downregulated	Induction of EMT with TGF-β results in low levels of SOX9, FOXA2, and GATA4	[44]
Pancreatic cancer	Mice	Overexpressed	p53-/- mice enhanced sphere formation, increased expression of the stemness regulator Bmi1 and Klf4, and pancreatic multipotent progenitor markers as Ptf1a, Pdx1, Cpa1, c-myc, Hnf1b and Sox9	[45]
Pancreatic cancer	FG and L3.6pl cell lines of pancreatic cancer under hypoxia	Overexpressed	Under hypoxia conditions, FG cell line expresses high levels of Sox9 and L3.6pl. Besides, WNT, CXCR4, retinoic acid, and FAK signaling pathways are regulated by Sox9 in L3.6pI	[46]
Pancreatic ductal adenocarcinoma and anaplastic pancreatic cancer	6 APC patients and 53 PDAC patients	Overexpressed	PDAC and APC have high expression of Sox9, being the expression of proteins related with CSCs and EMT process higher in APC samples than PDAC	[30]
Intraductal papillary mucinous neoplasm	19 IPMN cases	Overexpressed	SOX9-positive cells were confined to the lower portions of the papillary structures of IPMN	[47]
Solid pseudopapillary tumor	8 samples of SPT	Overexpressed	PDX1 and Sox9 are both expressed in the cytoplasm of SPT cell	[48]