From bile acids to yes-associated protein: A bidirectional switch for cholangiocarcinoma therapy

Table 1 Differential regulation of yes-associated protein signaling and pathological outcomes by specific bile acid species

Bile acid	Mechanism of action	Impact on yap	Pathological outcome	Ref.
TCA	S1PR2-MAPK	Activation1	Liver fibrosis; EAC progression	Sugihara et al[10]; Hu et al[11]; Yang et al[12]
GCA	Paracrine-CTGF	Activation1	Aggravates liver fibrosis	Yu et al[13]
GCDCA	Inhibits MST/LATS	Activation1	Drives CCA proliferation and invasion	Ilyas et al[9]
	Intracellular stress	Inhibition2	Biliary senescence and repair defects	Liu et al[14]
TUDCA	ER stress chaperone	Inhibition2	Restrains liver overgrowth	Yuan et al[15]
CDCA	IQGAP1-MST2	Activation1	Promotes HCC progression	Sasaki et al[16]
DCA	TGR5-cAMP	Inhibition2	Suppresses CCA growth (tumor switch)	Ilyas et al[9]; Mao et al[19]
	ABL1 axis	Activation1	Facilitates hepatic steatosis	Wu et al[17]
UDCA	TGR5-cAMP	Inhibition2	Suppresses CRC progression	Quinn et al[18]

¹Represents activation (nuclear accumulation/target gene expression).

²Represents inhibition (cytoplasmic retention/degradation).

TCA: Taurocholic acid; GCA: Glycocholic acid; GCDCA: Glycochenodeoxycholic acid; TUDCA: Tauroursodeoxycholic acid; CDCA: Chenodeoxycholic acid; DCA: Deoxycholic acid; UDCA: Ursodeoxycholic acid; MAPK: Mitogen-activated protein kinase; S1PR2: Sphingosine-1-phosphate receptor 2; CTGF: Connective tissue growth factor; MST/LATS: Mammalian Ste20-like kinases/Large tumor suppressor kinases; ER: Endoplasmic reticulum; MST2: Mammalian sterile 20-like kinase 2; IQGAP1: IQ motif containing GTPase activating protein 1; TGR5: Takeda G protein-coupled receptor 5; cAMP: Cyclic adenosine monophosphate; ABL1: Abelson tyrosine-protein kinase 1; EAC: Esophageal adenocarcinoma; CCA: Cholangiocarcinoma; HCC: Hepatocellular carcinoma; CRC: Colorectal cancer.