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Table 1 Comparison of the tumor phenotypes associated with deregulation of key regulators of mitophagy and general autophagy

From: Mitophagy and cancer

Gene (human/mouse) Linked human cancer Mouse model phenotype Reference
Mitophagy regulators    
Parkin Parkin located at chr. 6q25-q26 is significantly deleted in bladder, lung, breast, and ovarian cancer. Parkin null mice are susceptible to liver tumors; sensitized to irradiation-induced lymphomagenesis. [34,35,37]
BNIP3/Bnip3 BNIP3 is up-regulated in DCIS; epigenetically silenced in hematologic, liver, lung, colorectal, and pancreas cancer. Knockdown of BNIP3 promotes metastasis in an orthotopic mouse model of breast cancer. [86-91,100]
BNIP3L/Bnip3L (NIX/Nix) NIX is up-regulated in DCIS correlating with hypoxia. Knockdown of NIX promotes tumorigenicity in xenograft model. [64,86,87]
Autophagy regulators    
BECN1/Becn1 Mono-allelic deletion BECN1 in breast, ovarian, and prostate cancer, although linkage to BRCA1 calls significance of BECN1 deletion into question. Becn1 heterozygotes are predisposed to lymphoma, hepatocellular carcinoma, and other cancers; Becln1 deficiency promotes tumor growth in xenografts. [124-127]
p62/SQSTM1 p62/SQSTM1 amplification on chr.5q linked to clear cell renal cell carcinoma. Over-expressed in lung, breast and prostate cancer. p62-null mice resistant to Ras-driven lung tumorigenesis. Loss of p62 reduces liver tumorigenesis in Atg7-deficient mice and other models. [128-130]
ATG5/Atg5 Not reported. Deletion of Atg5 promotes early-stage tumor growth in K-Ras driven lung and pancreas cancers but inhibits progression to malignancy. [109,111]
ATG7/Atg7 Silenced in HNSCC. Deletion of Atg7 promotes early-stage tumor growth in K-Ras and B-Raf-driven lung and K-Ras-driven pancreas cancers but inhibits progression to malignancy. [108-110,131]
FIP200 (RB1CC1) Inactivating truncation mutations found in human breast cancers leads to repression of the RB tumor suppressor. Loss of FIP200 inhibits primary tumor growth and metastasis in the MMTV-PyVT mouse model of mammary tumorigenesis in a p62-dependent manner. [116,132]