Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly

Table 3 Implications of defects in adenosine triphosphate synthase subunits on bioenergetic alterations and the development or progression of gastrointestinal cancer

Type	Gene	Type of defect	Consequence	Model	Ref.
GC	ATP5F1B	Increased in tumor	Higher ATP5B expression correlated with poor prognosis. Over-expression of ATP5F1B increased intracellular and extracellular ATP levels, cell proliferation, migration, and invasion	GC patient, cell line, and xeno-transplantation mouse model	[107]
GC	ATP5F1B	Reduced in tumor	Reduced ATP5F1B expression correlated with elevated glycolytic enzyme levels	GC patient	[108]
HCC	ATP5F1B	Reduced in tumor	Reduced ATP5F1B expression correlated with impaired OXPHOS	HCC patient	[109,110]
ESCA	ATP5F1B	Reduced in tumor	Reduced ATP5F1B expression correlated with elevated glycolytic enzyme levels	ESCA patient	[108]
CRC	ATP5F1B	Reduced in tumor	Reduced ATP5F1B expression correlated with poor prognosis in CRC patients	CRC patient	[109]
PAC	ATP5F1B	Reduced in tumor	Unknown	PAC patient and cell line	[111]
CRC	ATP5F1A	Increased in liver metastasized tumor	Silencing of ATP5F1A inhibited cell invasion and reduced cell proliferation in CRC cancer cells	CRC patient and cell line	[112]
CRC	ATP5F1E	Increased in tumor	Higher ATP5E levels correlated with poor prognosis. Silencing of ATP5F1E inhibited cancer cell migration and invasion in vitro, and distal metastasis in vivo	CRC patient, cell line, and tail vein injected mouse model	[113]
CRC	ATP5F1D	Increased in liver metastasized tumor	Higher ATP5F1D expression correlated with poor prognosis, and silencing of ATP5F1D inhibited cell invasion	CRC patient and cell line	[112]

ATP: Adenosine triphosphate; GI: Gastrointestinal; ESCA: Esophageal cancer; GC: Gastric cancer; HCC: Hepatocellular carcinoma; CCA: Cholangiocarcinoma; PAC: Pancreatic cancer; CRC: Colorectal cancer; ATP5F1A: ATP synthase F1 subunit alpha; ATP5F1B: ATP synthase F1 subunit beta; ATP5F1D: ATP synthase F1 subunit delta; ATP5F1E: ATP synthase F1 subunit epsilon.