Biliary tract cancer stem cells - translational options and challenges

Table 2 Overly active pathways associated with cancer stem cell-like phenotype in biliary tract cancer specimens

Pathway	Component	Tissue	Outcome	Ref.
Hh	GLI1	GBC	↑ lymph node metastasis	[92,100]
	SHH	CC, GBC	↑ grade (by trend)	[92,100,101]
	SMO	GBC		[92]
JAK / STAT	STAT3	CC, IHC	↑ tumor size, ↑ metastasis, ↑ vascular invasion, ↓ survival, poor histological differentiation	[102,103]
mTOR	mTOR	BTC	↓ survival	[104]
	pmTOR1	GBC	↓ survival	[105]
NOTCH	NOTCH 1	EHC	poor histological differentiation, ↓ survival, ↑ tumor grade, ↑ Cyclin E	[86,87]
	NOTCH 2	EHC	↓ survival	[86]
	NOTCH 3	EHC	↓ survival, ↑ tumor grade, ↑ Cyclin E	[86,87]
	NOTCH 4	EHC		[86]
	HES-1	EHC	↓ survival	[86]
Wnt	β-catenin	CC	↑ metastasis	[91]2

¹Phosphorylated mTor;

²In this study, no non-tumor control samples were used as control. CC: Cholangiocarcinoma; EHC: Extrahepatic cholangiocarcinoma; GBC: Gallbladder cancer; IHC: Intrahepatic cholangiocarcinoma.