Tumor Suppression and Promotion by Autophagy

Table 1

Summary of oncogenes and tumor suppressors involved in autophagy regulation.

Oncogenes	Role in autophagy	Evidences of oncogenesis	Reference
AKT1	Upstream inhibitor of autophagy via mTOR activation	Gain-of-function mutations in several cancer types	[36]
BCL-2, BCL-XL	Sequester Beclin-1 into inactive complexes	Overexpressed in several cancer types	[37]
PI3K	Upstream inhibitors of autophagy via AKT1 activation	Gain-of-function mutations in many cancer types	[36, 38]
Ras	Upstream inhibitors of autophagy via mTOR activation	Hyperactivated in several cancer types	[37]
Tumor suppressors	Role in autophagy	Evidences of tumor suppression
ATG4	Converts LC3 into LC3 I during stress conditions	Mutations in ATG4C increase susceptibility to carcinogens	[39]
ARHI/DIRAS3, PTEN	Relieve autophagy inhibition mediated by PI3K-AKT1	Downregulated in ovarian cancer	[36, 40]
Beclin-1, p150	Required in the nucleation complex for autophagy initiation	Deleted in breast, ovarian, and prostate cancer	[41]
BH3-only proteins	Relieve autophagy inhibition mediated by BCL-2/BCL-XL	Mutated or silenced in many cancer types	[42–44]
UVRAG, BIF1	Positive regulator of the nucleation complex	Deleted or downregulated in colorectal cancer	[45]
DAPK1	Relieve autophagy inhibition mediated by BCL-2/BCL-XL	Silenced in many tumor types	[46]
LKB1/STK11	Promotes autophagy via AMPK activation	Mutated in Peutz-Jeghers syndrome and non-small cell lung carcinomas	[47, 48]
NF1	Relieve autophagy inhibition mediated by Ras	Mutated in neurofibromatosis, juvenile myelomonocytic leukemia	[37]
RAB7A	Modulates endosomal trafficking involved in autophagosome maturation	Rearranged in leukemia, deleted in solid tumors	[49]
TSC1, TSC2	Stimulate Rheb GTPase, thus inhibiting the PI3K-AKT1-mTOR pathway	Mutated in TSC	[50]